Department of Zoology, B N College, Patna University , Patna 800004, Bihar India.

Corresponding author email: sblal1990@gmail.com

Article Publishing History

INTRODUCTION

The term “diabetes mellitus” refers to a collection of metabolic diseases characterised by elevated blood glucose levels brought on by deficiencies in either the secretion or the function of insulin (Ganie and  Kotwal, 2012). Based on its pathophysiology, diabetes mellitus can be divided into three groups (IDF , 2013). An auto-immune response is the cause of type 1 diabetes (  Liu ,et al.; 2017). Another subtype found in pregnant women is gestational diabetes mellitus. Insulin sensitivity and declining beta cell insulin production are the root causes of type 2 diabetes (Yoshihara , et al.; 2014). Numerous recorded pieces of evidence support the idea that pancreatic beta cell loss plays a part in the onset of diabetes, (Alhawiti ,et.al;2017 Sanyaolu et al 2023).

Thioredoxin-interacting protein, or TXNIP for short, is a protein that regulates metabolism and is present in key organs such as the liver, skeletal muscles, and adipose tissues. TXNIP are proteins that belong to the alpha arrestin family. TXNIP interacts with Thioredoxins (TXN1 and TXN2), causing them to become less active. Through controlling adipogenesis, peripheral glucose absorption, beta cell activity, and other processes, TXNIP is crucial for the regulation of glucose and lipid metabolism. Insulin sensitivity is decreased and pancreatic beta cell death is caused by overexpression of TXNIP (Alhawiti , et al; 2017).

The TXNIP protein binds to TXN1, interfering with TXN1’s capacity to decrease oxidised protein, leading to oxidative stress and increased apoptotic possibilities. After migrating to the mitochondria, TXNIP competes with apoptosis signal regulating kinase 1 (ASK-1) to interact with TXN2, causing ASK-1 to be released. ASK-1 frequently binds to TXN2, inhibiting its activity (Yoshihara , et al.; 2014). Pancreatic beta cells’ apoptotic signalling cascade is triggered when the released ASK-1 is phosphorylated and activated as a result of TXNIP activity. Diabetes is primarily caused by beta cell dysfunction and reduced insulin production (Wondafrash , et al; 2020 Sanyaolu et al 2023).

A non-transmembrane enzyme called protein-tyrosine phosphatase 1B (PTP1B) is present on the endoplasmic reticulum (ER). Its importance comes from the fact that it negatively regulates both insulin and leptin signalling. Insulin receptor substrate proteins, also known as PTP1B, are the main substrates of the insulin receptor (IR) and are dephosporylated, or to put it another way, free of a phosphate group. PTP1B in leptin removes phosphate from JAK2, a tyrosine kinase known as Janus kinase 2. It has lately been discovered to be an important factor in the development of tumours and has been connected more directly to breast cancer. It is also considered a possible pharmacological target since its blockage may prevent type 2 diabetes, obesity, and some types of cancer. Because of its highly conserved positively charged active site pocket, protein tyrosine phosphatase 1B (PTP1B) is a useful target for the treatment of type 2 diabetes and obesity.

However, PTP1B is difficult to target for drug discovery. Significant progress has been achieved in the creation of highly potent and specific PTP1B inhibitors that bind to both the active and catalytic sites. To enhance the pharmacological characteristics of PTP1B inhibitors, a number of approaches are being investigated (Rohan  et al 2011). In addition to being a therapeutic target for the treatment of insulin resistant conditions including obesity and type 2 diabetes mellitus, protein tyrosine phosphatase 1B (PTB1B) is becoming more and more important in the pathogenesis of the resistance to insulin in diabetes mellitus (Radhika et al,2012). Moreover, PTP1B contributes to the suppression of leptin and insulin signalling. Consequently, PTP1B inhibitors offer therapeutic potential for the treatment of Type II diabetes as well as obesity. There is persuasive evidence that small molecule PTP1B inhibitors may be helpful in managing insulin resistance early on, resulting in a T2DM and obesity preventive strategy (Rao  et al 2006).

According to Ayurvedic research, the flower of Catharanthus roseus is said to treat diabetes. Several laboratory investigations have shown that Catharanthus roseus extracts derived from various plant components, such as the root, leaf, flower, and stem, have hypoglycemic action. Throughout India, people have been using the ancient medicinal plant Catharanthus roseus to cure diabetes. Patients with diabetes mellitus are given various plant components, such as leaves, flowers, and stems ( Jayanthi et al 2010). Flowers of Catharanthus roseus include numerous bioactives such as Petunidin, Hirsutidin, Catharanthine, and Vindoline. Bioactives are a category of natural compounds with varying polyphenolic structures that have anti-oxidant, anti-diabetic, and anti-aging properties (Saul et al 2009).

Other phenolic compounds, including petunidin, are naturally occurring polyphenols that preserve pancreatic beta cells, promote their growth, lower beta cell death, and reduce oxidative stress, all of which aid in the prevention and management of Type 2 Diabetes Mellitus ( Sun, et al; 2020). Identifying targets and predicting innovative medications In-silico approaches have been quite important (Wadood et al., 2013). With the use of bioinformatics tools and AutoDock Tools to assess the docking score, the current work examined the bioactive from Catharanthus roseus inhibitory effect on TXNIP and PTP 1B protein.

TXNIP and PTP 1B protein retrieval, Ligand preparation  and  active site prediction: The crystal structure of the TXNIP and PTP 1B proteins was obtained from the Protein Data Bank of the Research Collaboratory for Structural Bioinformatics (www.rcsb.org/pdb). ADT was used to add hydrogen bonds & Kollman charges to the obtained protein structure. The structures of Petunidin, Hirsutidin, Catharanthine, and Vindoline, as well as the control medication Rosiglitazone, were obtained from PubChem (https://pubchem.ncbi.nlm.nih.gov) in canonical SMILES. ChemSketch was used to build and optimise 3D structures. The compound structures were stored as MDL mol files (.mol). The MDL mol files were then translated to PDB format via the Open Babel molecular converter ( Boyle et al 2011).

Evaluation of Molecular Properties and Ligands ADMET prediction studies for the chemicals: The compounds’ physiochemical and pharmacological characteristics were examined using the the “SwissADME” an implement  offered by Swiss Institute of Bioinformatics ( www.swiss adme.ch) for  Properties such as molecule size, rotatable bond, logP, and hydrogen bond donor and acceptor properties were calculated. The selected ligands were examined for membrane permeability, bioavailability, distribution, metabolism, and adsorption (Lipinski’s rule of 5) ( Lipinski et al 2001, Jarrahpour, et al 2012). Compound pharmacokinetic properties was predicted using the web server PkCSM (unimelb.edu.au)( Pires et al 2015). It expects several parameters based on specific qualities.

These factors include absorption, distribution, metabolism, and excretion, which help us determine a drug’s pharmacokinetics. Drug absorption can be anticipated using variables such as CaCO2 and skin permeability, intestinal absorption, and P-glycoprotein substrate or inhibitor. The drug’s distribution was predicted using factors that include volume distribution (VD), permeability of the central nervous system (CNS), and the blood brain barrier (BBB). Metabolism was determined using the Cytochrome P450 model. The drug’s excretion was measured by its total clearance, renal substrate

Molecular docking: To determine the affinity, the AutoDock Tool was used to dock Petunidin, Hirsutidin, Catharanthine, and Vindoline from C. roseus, as well as the control Rosiglitazone, against TXNIP and PTP 1B proteins (GM Morris et al, 1998). Kohlman charges and polar hydrogen atoms were introduced to the 3D TXNIP and PTP 1B macromolecular structure. The protein-ligand interaction of , Hirsutidin, Petunidin,  Catharanthine, Vindoline and the control Rosiglitazone against TXNI and PTP 1B P protein was visualised with Molecular graphics laboratory (MGL)/Chimera X tool.

The structures of ligand under investigation were processed in Chimera to obtain a minimum energy conformer through 10 steepest descent steps followed by 100 conjugate gradient steps. The stabilized ligand conformers were also saved in .pdb format. The protein-ligand docking complexes were performed using AutoDock 4.2 (Forli et al.2016,Morris et al 2009). The LGA method was employed. A grid point spacing of 1.000 Å was set, centered on x= 86, y= 86, and z= 86Å for the TXNIP protein docking.  And a grid point spacing of 0.500 Å was set, centered on x= 60, y= 60, and z= 60Å for the PTP1B protein docking. The coordinates of central grid point of maps (-14.025, 1.890, 40.242 Å) for TXNIP protein docking and (-1.591, 62.698, 2.975 Å) was used for PTP1B (2BGD) protein docking.

RESULTS AND DISCUSSION

Table 1. PubChem id , Molecular Formula and Smiles of the bio
actives of Catharanthus roseus & Rosiglitazone

Compound	PubChem id	Molecular Formula	Smiles
Petunidin	441774	C16H13O7+	COC1=CC(=CC(=C1O)O)C2=[O+]C3=CC(=CC(=C3C=C2O)O)O
Hirsutidin	441694	C18H17O7+	COC1=CC(=C2C=C(C(=[O+]C2=C1)C3=CC(=C(C(=C3)OC)O)OC)O)O
Catharanthine	5458190	C21H24N2O2	CCC1=CC2CC3(C1N(C2)CCC4=C3NC5=CC=CC=C45)C(=O)OC
Vindoline	260535	C25H32N2O6	CCC12C=CCN3C1C4(CC3)C(C(C2OC(=O)C)(C(=O)OC)O)N(C5=C4C=CC(=C5)OC)C
Rosiglitazone	77999	C18H19N3O3S	CN(CCOC1=CC=C(C=C1)CC2C(=O)NC(=O)S2)C3=CC=CC=N3

Molecular compound selected for the Phyto chemical from the Catharanthus roseus have less than 500 daltons of molecular weight which is in accordance with the Lipinski rule of five and is also comparable with the control drug Rosiglitazone. Octanol- water partition coefficient (log P) was found to be less than 5 for all Phyto compounds used in this study. Number of hydrogen bond acceptors for Petunidin, Hirsutidin, and Rosiglitazone was calculated to be as 6  and 3 hydrogen bond acceptors for Catharanthine and 8 hydrogen bond acceptors Vindoline. Catharanthine, Vindoline and Rosiglitazone have only one hydrogen bond donor whereas Petunidin and Hirsutidin have 5 and 3  donors bond respectively. Surface Area  was least for Petunidin and highest for  Vindoline  satisfying the  Lipinski rule of five for prediction as an ideal drug candidate for treatment of T2D.

Figure 1: Molecular formula and  2D Structure  of the bio actives
of Catharanthus roseus & Rosiglitazone

Figure 2: The ribbon shaped 3D structure  of the  Thioredoxin
interacting protein & Tyrosine phosphatase

Molecular properties of the bio actives of Catharanthus roseus & Rosiglitazone

Table 2. Molecular properties of the bio actives of Catharanthus roseus & Rosiglitazone

MOLECULAR PROPERTIES
PROPERTY	Petunidin	Hirsutidin	Catharanthine	Vindoline	Rosiglitazone
Molecular Weight	317.273	345.327	336.435	456.539	357.435
LogP	2.9175	3.5235	3.1753	1.6413	2.4909
#Rotatable Bonds	2	4	2	4	7
#Acceptors	6	6	3	8	6
#Donors	5	3	1	1	1
Surface Area	129.425	142.793	147.394	193.630	150.126

ADMET properties of the bio actives of Catharanthus roseus & Rosiglitazone: ADMET properties of the bioactives such as Petunidin, Hirsutidin, Catharanthine, and Vindoline from Catharanthus roseus & Rosiglitazone ,  showed satisfactory results on the various parameters used to evaluate the ADMET properties. Absorption parameter Catharanthine violated the Caco2 permeability as it have 1.114 log cm/s permeabilities which should be not more than 0.90 log cm/s. Intestinal absorption (human) is grater than 30% for all the bioactive such as Petunidin, Hirsutidin, Catharanthine, and Vindoline from Catharanthus roseus & Rosiglitazone which showed good results on this parameter. Skin Permeability of Vindoline among all the Phyto chemicals and Rosiglitazone was highest with log Kp cm/h of -3.088 but all the bioactive such as Petunidin, Hirsutidin, Catharanthine, and Vindoline from Catharanthus roseus & Rosiglitazone showed violation and are greater than -2.5 log Kp cm/h.

 P-glycoprotein substrate was formed by all the bio compounds whereas Rosiglitazone have not formed  P-glycoprotein substrate and  P-glycoprotein II inhibitor. Only Vindoline had all the  P-glycoprotein substrate , P-glycoprotein I inhibitor and  P-glycoprotein II inhibitor during PkCSM  assessment. VDss (human) was low for Hirsutidin and Rosiglitazone with -0.215 L/kg and – 183 L/kg. Fraction unbound (human) for all the phyto chemical and synthetic drug was considered safe while BBB permeability and  CNS permeability was only satisfactory for Catharanthine during the analysis . CYP3A4 substrate was not formed by Petunidin  whereas  CYP2C9 inhibitior was not produced by Catharanthine and CYP2C9 inhibitior by Hirsutidin. CYP3A4 inhibitior none of the natural or synthetic compound forms CYP3A4 inhibitior at the metabolism parameters of pharmacokinetic . On excretion parameters Total Clearance and Renal OCT2 substrate Catharanthine performs poorly . AMES toxicity was also positive for only Catharanthine  while Hepatotoxicity was positive for  Rosiglitazone  only.

Table 3. ADMET properties of the bio actives of Catharanthus roseus & Rosiglitazone

ABSORPTION
PROPERTY	Petunidin	Hirsutidin	Catharanthine	Vindoline	Rosiglitazone
Water solubility	-2.943	-3.583	-3.399	-3.414	-3.762
Caco2 permeability	-0.47	0.041	1.114	0.222	0.964
Intestinal absorption (human)	84.429	84.297	93.597	96.576	93.757
Skin Permeability	-2.735	-2.735	-2.932	-3.088	-2.844
P-glycoprotein substrate	Yes	Yes	Yes	Yes	No
P-glycoprotein I inhibitor	No	No	Yes	Yes	Yes
P-glycoprotein II inhibitor	No	Yes	No	Yes	No
DISTRIBUTION
VDss (human)	0.837	-0.215	1.485	0.542	-0.183
Fraction unbound (human)	0.182	0.054	0.312	0.265	0.078
BBB permeability	-1.415	-1.292	0.287	-0.261	-0.727
CNS permeability	-3.48	-3.018	-1.939	-3.375	-2.785
METABOLISM
CYP2D6 substrate	No	No	Yes	No	No
CYP3A4 substrate	No	Yes	Yes	Yes	Yes
CYP1A2 inhibitior	Yes	Yes	No	No	No
CYP2C19 inhibitior	No	Yes	No	No	Yes
CYP2C9 inhibitior	No	Yes	No	No	No
CYP2D6 inhibitior	No	No	Yes	No	No
CYP3A4 inhibitior	No	No	No	No	No
EXCRETION
Total Clearance	0.647	0.746	1.167	0.511	0.107
Renal OCT2 substrate	No	No	Yes	No	No
TOXICITY
AMES toxicity	No	No	Yes	No	No
Max. tolerated dose (human)	0.534	0.657	-0.572	-0.661	0.066
hERG I inhibitor	No	No	No	No	No
hERG II inhibitor	No	No	Yes	Yes	No
Oral Rat Acute Toxicity (LD50)	2.459	2.32	3.139	3.225	2.692
Oral Rat Chronic Toxicity (LOAEL)	2.45	1.68	1.488	1.599	1.415
Hepatotoxicity	No	No	No	No	Yes
Skin Sensitisation	No	No	No	No	No
T.Pyriformis toxicity	0.294	0.341	0.445	0.295	1.038
Minnow toxicity	2.463	1.626	-0.727	1.365	1.63

Molecular docking analysis: Binding energy (kcal/mol) and inhibition constant (µM) values of the docking complexes of proteins Tyrosine phosphatase PTP1B(2BGD) with Hirsutidin calculated by molecular docking study was -7.62 kcal/mol and 2.61 µM suggestive of its preference over the synthetic drug  Rosiglitazone whose Binding energy was -7.12 kcal/mol with inhibition constant at 6.02 µM . All  the bio actives selected from Catharanthus roseus  performs good in comparison to the Rosiglitazone  at parameters like Binding energy (kcal/mol) and inhibition constant (µM) values during Molecular docking analysis of the docking complexes of proteins Tyrosine phosphatase PTP1B(2BGD)   as shown in table no 4.

All  the bio actives selected from Catharanthus roseus  performs good in comparison to the Rosiglitazone  at the  parameters like Binding energy (kcal/mol) and inhibition constant (µM) values during Molecular docking analysis of the  docking complexes of proteins Thioredoxin interacting protein TXNIP (4LL1) as shown in table no 4. Binding energy (kcal/mol) and inhibition constant (µM) values of the docking complexes of proteins Thioredoxin interacting protein TXNIP (4LL1) with Catharanthine calculated by molecular docking study was -5.8 kcal/mol and 56.12 µM suggestive of its preference over the synthetic drug  Rosiglitazone whose Binding energy was -7.12 kcal/mol with inhibition constant at 6.02 µM.

Table 4.  Binding energy (kcal/mol) and inhibition constant (µM) values of the docking
complexes of proteins with ligands calculated by molecular docking study.

Protein	Petunidin		Hirsutidin		Catharanthine		Vindoline		Rosiglitazone
	(kcal/ mol)	µM	(kcal/ mol)	µM	(kcal/ mol)	µM	(kcal/ mol)	µM	(kcal/ mol)	µM
TXNIP (4LL1)	-4.04	1100	-4.67	378.3	-5.8	56.12	-3.51	2650	-4.75	327.53
PTP1B(2BGD)	-6.81	10.11	-7.62	2.61	-5.73	63.18	-4.79	308.1	-7.12	6.02

Figure 3: The docking complexes of proteins Tyrosine phosphatase PTP1B (2BGD) with
Catharanthine calculated by molecular docking study.

Figure 4: The docking complexes of proteins Tyrosine phosphatase PTP1B(2BGD)
with Hirsutidin calculated by molecular docking study.

Figure 5: The docking complexes of proteins Tyrosine phosphatase PTP1B(2BGD)
with Petunidin calculated by molecular docking study.

Figure 6: The docking complexes of proteins Tyrosine phosphatase PTP1B(2BGD)
with Vindoline calculated by molecular docking study.

Figure 7: The docking complexes of proteins Tyrosine phosphatase PTP1B(2BGD)
with Rosiglitazone calculated by molecular docking study.

The docking complexes of proteins Tyrosine phosphatase PTP1B(2BGD) with Catharanthine has three van der waals bond at PHE  182, ILE 219  and GLN  262 ,  two Alkyl bonds at ALA 217 and  VAL 49  with a single Pi-Pi  Bond at TYR 46, Hydrogen bond at AGR 47  and a salt bridge at ASP 48. The docking complexes of proteins Tyrosine phosphatase PTP1B(2BGD) with Hirsutidin had five conventional hydrogen bond at ASP 48, GLN 262, SER 216 , ARG 221 and GLU 115 followed by  Van der waals active forces at ARG 47, GLY 218, ILE 219 and GLY 220.  The complex also  do have  carbon hydrogen bond at ASP 181 and LYS 120,  Pi- Pi bond at PHE 182 and TYR 46  , Alkyl bond at ALA 217 & CYS 215 followed by Pi sigma bond at VAL 49.Tyrosine phosphatase PTP1B(2BGD) on docking with  Petunidin produces 6 conventional hydrogen bond at ASP 48, SER 216, AGR 221, GLU 115, GLN 262 and  ALA 217 followed by Pi sigma bond at VAL 49. The docking complex also have  Pi-Pi bonds at TYR 46 and PHE 182.

The complex between Tyrosine phosphatase PTP1B(2BGD) and Petunidin also have five Van Der Waals forces site at  GLY 220, GLY 128, ASP181, ARG 47 and LYS 120 with  an alkyl bond at CYS 215.Tyrosine phosphatase PTP1B(2BGD) on interaction with Vindoline produces Pi- alkyl bonds at MET 258, ALA 217, VAL 49 AND ILE 219  and a salt bridge at ASP 48. Only one conventional hydrogen bond at ARG 24 with four Van der waals site at ARG 46, PHE 182, ARG 254 and TYR 46. The complex also do have two Carbon Hydrogen bonds at TYR 20 and GLN 262.The docking complexes of proteins Tyrosine phosphatase PTP1B(2BGD) with Rosiglitazone  had a Pi sulphur bond at PHE 182 and Pi-Pi bonds at PHE 182 and TYR 46 . The Interaction studies  also reveals that  there is also an unfavourable donor at AGR 221 with  nine Van Der Waals site of interactions at SER 222, ASP 181, AGR 47, ASP 48, VAL 49, LYS 120, SER 216 and  GLN 262.  The docking complexes of proteins Tyrosine phosphatase PTP1B(2BGD) with Rosiglitazone had seven conventional hydrogen bonds positioned at  GLY 218, GLY 220, ALA 217, ILE 219, CYS 215, GLN 266 and PHE 182.

Figure 8: The docking complexes of proteins Thioredoxin interacting protein TXNIP (4LL1)
with Catharanthine calculated by molecular docking study.

Van Der Waals interactions were active at TYR 72, GLN 226, GLY 225, THR 227, PRO 106, GLN 107, GLN 226, THR 227, LEU 222, PHE 103, LEU 270, THR 69 and ARG 71 in the docking complexes of proteins Thioredoxin interacting protein TXNIP (4LL1) with Catharanthine. The docking complexes of proteins Thioredoxin interacting protein TXNIP (4LL1) with Catharanthine had conventional hydrogen bond at GLU 104 and GLY 225 with Alkyl bond at PRO 106 and Leu 70. Hirsutidin on interaction with TXNIP produces conventional hydrogen bond at GLY 266 , THR 66 and Lys 64   and carbon hydrogen bond at SER 298 and ILE 296. PRO 262, ILE 260, ILE 269, THR 274 was the site for Pi- alkyl bond in the docking complexes of proteins Thioredoxin interacting protein TXNIP (4LL1) with Hirsutidin.

Figure 9 : The docking complexes of proteins Thioredoxin interacting protein TXNIP (4LL1)
with Hirsutidin calculated by molecular docking study.

Figure 10: The docking complexes of proteins Thioredoxin interacting protein TXNIP (4LL1)
with Petunidin calculated by molecular docking study.

Figure 11: The docking complexes of proteins Thioredoxin interacting protein TXNIP (4LL1)
with Vindoline calculated by molecular docking study.

Figure 12: The docking complexes of proteins Thioredoxin interacting protein TXNIP (4LL1)
with Rosiglitazone calculated by molecular docking study

Van Der Waals interactions in the docking complexes of protein TXNIP (4LL1) with Hirsutidin were at GLN 65, GLY 297, VAL 272 , ASN 268, SER 267 and AGR 71.Thioredoxin interacting protein ,TXNIP (4LL1) on interactions with Petunidin had Pi Anion bond at ASP 74 with Pi alkyl bond at LEU 77. Conventional hydrogen bonds were represented by THR 227, ASP 74, GLY 102, LYS 100 and LEU 77.Van Der Waals interactions were active at GLN 226, LYS 228, THR 72, PHE 101, LEU 76, THR 231 and VAL 229 in the docking complexes of proteins Thioredoxin interacting protein TXNIP (4LL1) with Petunidin.

The docking complexes of proteins Thioredoxin interacting protein TXNIP (4LL1) with Vindoline calculated by molecular docking study showed Pi Anion or active charge at GLU 144 with conventional hydrogen bond at ASN 142. There was also Van Der Waals interactions at VAL 20, GLU 18, LYS 19 , PHE 143 and a carbon hydrogen bond at PRO 17. Thioredoxin interacting protein TXNIP (4LL1) on interaction with Rosiglitazone had three conventional hydrogen bonds at ARG 71, GLU 104 and AGR 271 with two Carbon hydrogen  bond at THR 227 AND GLY 225. Van Der Waals forces were active at LEU 70, PHE 103, TYR 72, GLN 226, GLY 225, THR 220, LEU 222, LEU 270  and TYR 69.

The docking complexes of proteins Thioredoxin interacting protein TXNIP (4LL1) with Vindoline calculated by molecular docking study showed Pi Anion or active charge at GLU 144 with conventional hydrogen bond at ASN 142. There was also Van Der Waals interactions at VAL 20, GLU 18, LYS 19 , PHE 143 and a carbon hydrogen bond at PRO 17. Thioredoxin interacting protein TXNIP (4LL1) on interaction with Rosiglitazone had three conventional hydrogen bonds at ARG 71, GLU 104 and AGR 271 with two Carbon hydrogen  bond at THR 227 AND GLY 225. Van Der Waals forces were active at LEU 70, PHE 103, TYR 72, GLN 226, GLY 225, THR 220, LEU 222, LEU 270  and TYR 69.

CONCLUSION

The molecular docking revealed that Hirsutidin had a lower binding energy (-7.62 Kcal/mol) on the TP1B receptor than Catharanthine on the TXNIP receptor (-5.8 Kcal/mol) when compared with synthetic medicines  Rosiglitazone which had binding energy (-7.12 Kcal/mol) & (- 4.75 Kcal/mol) on the TP1B and TXNIP receptors. When evaluated using different parameters, the ADMET qualities of bioactive from Catharanthus roseus, such as Vindoline, Hirsutidin, Petunidin, and Catharanthine, as well as Rosiglitazone, demonstrated satisfactory findings. ADMET properties like  a AMES toxicity was positive for only Catharanthine  whereas  on Hepatotoxicity parameters Rosiglitazone was found to be positive .Finally, the predictions indicated that Hirsutidin or Catharanthine might represent a promising lead option for T2D prevention. It is proposed that the current prediction be validated with experimental toxicology & pharmacological assays in the future.

Conflict of interest: The authors have no conflict of interest.

Funding: Authors did not receive any funding for this work.

Data Availability: Data will be available on request.

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