Login Register Cart 0
Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Investigation on Anti-diabetic Efficacy of a Cucurbitaceae Food Plant from the North-East Region of India: Exploring the Molecular Mechanism through Modulation of Oxidative Stress and Glycosylated Hemoglobin (HbA1c)

Author(s): Sandipan Jana, Srijon Gayen, Barun Das Gupta, Seha Singha, Jayashree Mondal, Amit Kar, Abhimanyu Nepal, Suparna Ghosh, Rajan Rajabalaya, Sheba R. David, Ashok Kumar Balaraman, Asis Bala, Pulok Kumar Mukherjee and Pallab Kanti Haldar*

Volume 24, Issue 2, 2024

Published on: 19 September, 2023

Page: [220 - 234] Pages: 15

DOI: 10.2174/1871530323666230907115818

Price: $65

Abstract

Background: The medicinal plants of the Cucurbitaceae family, such as Solena heterophylla Lour. fruits, have significant ethnobotanical value and are readily accessible in North East India.

Aims: We conducted a study on Solena heterophylla Lour. fruits to evaluate their anti-diabetic activity in vivo, standardize their HPTLC, and profile their metabolites using LC-QTOF-MS. We aimed to explore the molecular mechanism behind their effects on oxidative stress and glycosylated hemoglobin (HbA1c).

Methods: Firstly, the ethyl acetate fraction of Solena heterophylla Lour. fruits was standardized using Cucurbitacin B as a standard marker by conducting HPTLC evaluation. Next, we delved into analyzing metabolite profiling. In addition, the standardized fraction was utilized in an experimental study to investigate the molecular mechanism of action in an in vivo high-fat diet and a low dose of streptozotocin-induced diabetic model.

Results: We have reportedly identified 52 metabolites in the ethyl acetate fraction of Solena heterophylla (EASH). In the in vitro tests, it has been observed that this extract from plants possesses notable inhibitory properties against α-amylase and α-glucosidase. Solena heterophylla fruits with high levels of Cucurbitacin B (2.29% w/w) helped lower FBG levels in animals with EASH treatment. EASH treatment reduced HbA1c levels and normalized liver lipid peroxidation and antioxidant enzyme levels. SGOT, SGPT, and SALP serum enzyme levels also returned to normal.

Conclusion: Based on the current evaluation, it was found that EASH exhibited encouraging hypoglycemic effects in diabetic rats induced by a low dose of STZ and high-fat diet, which warrants further investigation.

« Previous Next »
Graphical Abstract

[1]
Janbaz, K.H.; Akhtar, T.; Saqib, F.; Imran, I.; Zia-Ul-Haq, M.; Jansakul, C.; De Feo, V.; Moga, M. Pharmacological justification of use of Solena heterophylla Lour. in gastrointestinal, respiratory and vascular disorders. J. Transl. Med., 2015, 13(1), 134.
[http://dx.doi.org/10.1186/s12967-015-0470-8] [PMID: 25925396]
[2]
Marles, R.J.; Farnsworth, N.R. Antidiabetic plants and their active constituents. Phytomedicine, 1995, 2(2), 137-189.
[http://dx.doi.org/10.1016/S0944-7113(11)80059-0] [PMID: 23196156]
[3]
Eddouks, M.; Bidi, A.; El Bouhali, B.; Hajji, L.; Zeggwagh, N.A. Antidiabetic plants improving insulin sensitivity. J. Pharm. Pharmacol., 2014, 66(9), 1197-1214.
[http://dx.doi.org/10.1111/jphp.12243] [PMID: 24730446]
[4]
Renner, S.; Pandey, A. The Cucurbitaceae of India: Accepted names, synonyms, geographic distribution, and information on images and DNA sequences. PhytoKeys, 2013, 20(0), 53-118.
[http://dx.doi.org/10.3897/phytokeys.20.3948] [PMID: 23717193]
[5]
Ramachandran, A.; Wan Ma, R.C.; Snehalatha,, C. Diabetes in Asia. Lancet, 2010, 375(9712), 408-418.
[http://dx.doi.org/10.1016/S0140-6736(09)60937-5] [PMID: 19875164]
[6]
Ganesan, K.; Rana, M.B.M.; Sultan, S. Oral Hypoglycemic Medications. In: StatPearls; StatPearls Publishing: Treasure Island, FL, 2023.
[7]
Modak, M.; Dixit, P.; Londhe, J.; Ghaskadbi, S.; Devasagayam, T.P.A. Indian herbs and herbal drugs used for the treatment of diabetes. J. Clin. Biochem. Nutr., 2007, 40(3), 163-173.
[http://dx.doi.org/10.3164/jcbn.40.163] [PMID: 18398493]
[8]
Sang, J.; Dhakal, S.; Lee, Y.; Cucurbitacin, B. Cucurbitacin B suppresses hyperglycemia associated with a high sugar diet and promotes sleep in Drosophila melanogaster. Mol. Cells, 2021, 44(2), 68-78.
[http://dx.doi.org/10.14348/molcells.2021.2245] [PMID: 33542166]
[9]
Kim, K.H.; Lee, I.S.; Park, J.Y.; Kim, Y.; An, E.J.; Jang, H.J.; Cucurbitacin, B. Cucurbitacin B induces hypoglycemic effect in diabetic mice by regulation of AMP-activated protein kinase alpha and glucagon-like peptide-1 via bitter taste receptor signaling. Front. Pharmacol., 2018, 9, 1071.
[http://dx.doi.org/10.3389/fphar.2018.01071] [PMID: 30298009]
[10]
Abdel-Hassan, I.A.; Abdel-Barry, J.A.; Tariq Mohammeda, S. The hypoglycaemic and antihyperglycaemic effect of Citrullus colocynthis fruit aqueous extract in normal and alloxan diabetic rabbits. J. Ethnopharmacol., 2000, 71(1-2), 325-330.
[http://dx.doi.org/10.1016/S0378-8741(99)00215-9] [PMID: 10904181]
[11]
Kumar, G.; Sudheesh, S.; Vijayalakshmi, N. Hypoglycaemic effect of Coccinia indica: Mechanism of action. Planta Med., 1993, 59(4), 330-332.
[http://dx.doi.org/10.1055/s-2006-959693] [PMID: 8372150]
[12]
Kameswararao, B.; Kesavulu, M.M.; Apparao, C. Evaluation of antidiabetic effect of Momordica cymbalaria fruit in alloxan-diabetic rats. Fitoterapia, 2003, 74(1-2), 7-13.
[http://dx.doi.org/10.1016/S0367-326X(02)00297-6] [PMID: 12628387]
[13]
Sherwani, S.I.; Khan, H.A.; Ekhzaimy, A.; Masood, A.; Sakharkar, M.K. Significance of HbA1c test in diagnosis and prognosis of diabetic patients. Biomark. Insights, 2016, 11, BMI.S38440.
[http://dx.doi.org/10.4137/BMI.S38440] [PMID: 27398023]
[14]
Davidson, J.A.; Liebl, A.; Christiansen, J.S.; Fulcher, G.; Ligthelm, R.J.; Brown, P.; Gylvin, T.; Kawamori, R. Risk for nocturnal hypoglycemia with biphasic insulin aspart 30 compared with biphasic human insulin 30 in adults with type 2 diabetes mellitus: A meta-analysis. Clin. Ther., 2009, 31(8), 1641-1651.
[http://dx.doi.org/10.1016/j.clinthera.2009.08.011] [PMID: 19808125]
[15]
Singha, S.; Biswas, S.; Dasgupta, B.; Kar, A.; Mukherjee, P.K. Standardization of some plants of the Cucurbitaceae family by a validated high-performance thin-layer chromatography method. J. Planar Chromatogr. Mod. TLC, 2020, 33(5), 463-472.
[http://dx.doi.org/10.1007/s00764-020-00061-w]
[16]
Fattahi, S.; Zabihi, E.; Abedian, Z.; Pourbagher, R.; Motevalizadeh Ardekani, A.; Mostafazadeh, A.; Akhavan-Niaki, H. Total phenolic and flavonoid contents of aqueous extract of stinging nettle and in vitro antiproliferative effect on hela and BT-474 cell lines. Int. J. Mol. Cell. Med., 2014, 3(2), 102-107.
[PMID: 25035860]
[17]
Goldar, W.A.; Jana, S.; Kumari, R.; Bhattacharya, S.; Haldar, P.K. Litsea cubeba fruit attenuates diabetes-associated metabolic complications in mice. Bull. Natl. Res. Cent., 2022, 46(1), 67.
[http://dx.doi.org/10.1186/s42269-022-00734-y]
[18]
Gupta, B.D.; Kar, A.; Narayan, S.; Thakur, C.P.; Mukherjee, P.K.; Haldar, P.K. Ultra‐performance liquid chromatography‐Quadrupole time‐of‐flight tandem mass spectrometry‐based metabolite profiling, quality evaluation, and marker analysis of Trachyspermum ammi (L.) Sprague by high‐performance thin‐layer chromatography. J. Sep. Sci., 2023, 46(10), 2200872.
[http://dx.doi.org/10.1002/jssc.202200872] [PMID: 36930465]
[19]
Sharma, A.; Katiyar, C.K.; Banerjee, S.; Chanda, J.; Kar, A.; Biswas, S.; Mukherjee, P.K. RP-HPLC and HPTLC methods for analysis of selected herbs used as complexion promoters in ayurveda and unani systems of medicine. J. AOAC Int., 2020, 103(3), 692-698.
[http://dx.doi.org/10.5740/jaoacint.19-0290] [PMID: 31619314]
[20]
Debnath, P.; Das, B.; Singha, S.; Kar, A.; Haldar, P.K.; Sharma, N.; Mukherjee, P.K. Quantification of cucurbitacin E in different varieties of melon (Cucumis melo L.) fruit through validated RP-HPLC method. Nat. Prod. Res., 2022, 24, 1-7.
[http://dx.doi.org/10.1080/14786419.2022.2136656] [PMID: 36278903]
[21]
Guidelines for the Testing of Chemicals/Section 4: Health Effects Test No. 425: Acute Oral Toxicity: Up-and-Down Procedure; Organisation for Economic Co-operation and Development Publishing: Paris, 2008.
[22]
Guex, C.G.; Reginato, F.Z.; de Jesus, P.R.; Brondani, J.C.; Lopes, G.H.H.; Bauermann, L.F. Antidiabetic effects of Olea europaea L. leaves in diabetic rats induced by high-fat diet and low-dose streptozotocin. J. Ethnopharmacol., 2019, 235, 1-7.
[http://dx.doi.org/10.1016/j.jep.2019.02.001] [PMID: 30721736]
[23]
Naskar, S. Comparative in vitro antioxidant activity of different parts of Cocos nucifera (Linn.) on reactive oxygen and nitrogen species. Int. J. Pharm. Pharm. Sci., 2011, 3, 104-107.
[24]
Zheng, H.; Whitman, S.A.; Wu, W.; Wondrak, G.T.; Wong, P.K.; Fang, D.; Zhang, D.D. Therapeutic potential of Nrf2 activators in streptozotocin-induced diabetic nephropathy. Diabetes, 2011, 60(11), 3055-3066.
[http://dx.doi.org/10.2337/db11-0807] [PMID: 22025779]
[25]
Willey, D.G.; Rosenthal, M.A.; Caldwell, S. Glycosylated haemoglobin and plasma glycoprotein assay by affinity chromatography. Diabetologia, 1984, 27, 56-61.
[http://dx.doi.org/10.1007/BF00253503] [PMID: 6468800]
[26]
Haldar, P.K.; Patra, S.; Bhattacharya, S.; Bala, A. Antidiabetic effect of Drymaria cordata leaf against streptozotocin–nicotinamide-induced diabetic albino rats. J. Adv. Pharm. Technol. Res., 2020, 11(1), 44-52.
[http://dx.doi.org/10.4103/japtr.JAPTR_98_19] [PMID: 32154158]
[27]
Jana, S.; Sarkar, N.; Chakraborty, M.; Kar, A.; Banerjee, S.; Bhattacharya, S.; Mukherjee, P.K.; Haldar, P.K. Combination synergy between β-carotene and lupeol against breast adenocarcinoma in vitro and in vivo using combination index. Phytomed. Plus., 2023, 3(1), 100392.
[http://dx.doi.org/10.1016/j.phyplu.2022.100392]
[28]
Skovsø, S. Modeling type 2 diabetes in rats using high fat diet and streptozotocin. J. Diabetes Investig., 2014, 5(4), 349-358.
[http://dx.doi.org/10.1111/jdi.12235] [PMID: 25411593]
[29]
Shah, A.D.; Langenberg, C.; Rapsomaniki, E.; Denaxas, S.; Pujades-Rodriguez, M.; Gale, C.P.; Deanfield, J.; Smeeth, L.; Timmis, A.; Hemingway, H. Type 2 diabetes and incidence of cardiovascular diseases: A cohort study in 1•9 million people. Lancet Diabetes Endocrinol., 2015, 3(2), 105-113.
[http://dx.doi.org/10.1016/S2213-8587(14)70219-0] [PMID: 25466521]
[30]
Zhang, M.; Lv, X.Y.; Li, J.; Xu, Z.G.; Chen, L. The characterization of high-fat diet and multiple low-dose streptozotocin induced type 2 diabetes rat model. Exp. Diabetes Res., 2008, 2008, 1-9.
[http://dx.doi.org/10.1155/2008/704045] [PMID: 19132099]
[31]
Wink, M. Modes of action of herbal medicines and plant secondary metabolites. Medicines, 2015, 2(3), 251-286.
[http://dx.doi.org/10.3390/medicines2030251] [PMID: 28930211]
[32]
Chakraborty, M.; Bala, A.; Bhattacharya, S. Hypoglycemic effect of ethyl acetate fraction of methanol extract from Campylandra aurantiaca rhizome on high-fat diet and low-dose streptozotocin-induced diabetic rats. Pharmacogn. Mag., 2018, 14(59s), s539-s545.
[33]
Peng, W.K.; Chen, L.; Boehm, B.O. Molecular phenotyping of oxidative stress in diabetes mellitus with point-of-care NMR system. NPJ Aging Mech. Dis., 2020, 6, 11.
[http://dx.doi.org/10.1038/s41514-020-00049-0]
[34]
Bala, A.; Roy, S.; Das, D.; Marturi, V.; Mondal, C.; Patra, S.; Haldar, P.K.; Samajdar, G. Role of glycogen synthase kinase-3 in the etiology of type 2 diabetes mellitus: A review. Curr. Diabetes Rev., 2022, 18(3), e300721195147.
[http://dx.doi.org/10.2174/1573399817666210730094225] [PMID: 34376135]
[35]
Panigrahi, G.; Panda, C.; Patra, A. Extract of Sesbania grandiflora ameliorates hyperglycemia in high fat diet-streptozotocin induced experimental diabetes mellitus. Scientifica, 2016, 2016, 1-10.
[http://dx.doi.org/10.1155/2016/4083568] [PMID: 27313954]
[36]
Kostecka-Gugała, A.; Kruczek, M.; Ledwożyw-Smoleń I.; Kaszycki, P. Antioxidants and health-beneficial nutrients in fruits of eighteen cucurbita cultivars: Analysis of diversity and dietary implications. Molecules, 2020, 25(8), 1792.
[http://dx.doi.org/10.3390/molecules25081792] [PMID: 32295156]
[37]
Ul Haq, F.; Ali, A.; Khan, M.N.; Shah, S.M.Z.; Kandel, R.C.; Aziz, N.; Adhikari, A.; Choudhary, M.I.; ur-Rahman, A.; El-Seedi, H.R.; Musharraf, S.G. Metabolite profiling and quantitation of cucurbitacins in cucurbitaceae plants by liquid chromatography coupled to tandem mass spectrometry. Sci. Rep., 2019, 9(1), 15992.
[http://dx.doi.org/10.1038/s41598-019-52404-1] [PMID: 31690753]
[38]
Bhandari, U.; Kumar, P. Protective effect of Trigonella foenum-graecum Linn. on monosodium glutamate-induced dyslipidemia and oxidative stress in rats. Indian J. Pharmacol., 2013, 45(2), 136-140.
[http://dx.doi.org/10.4103/0253-7613.108288] [PMID: 23716888]
[39]
(a) Larcan, A.; Lambert, H.; Laprevote-Heully, M.C.; Delorme, N. Light and electron microscopic study of hepatic lesions in the course of hyperlactatemia in diabetic patients. Diabetes Metab., 1979, 5, 103-112.;
(b) Navarro, C.M.; Montilla, P.M.; Martin, A.; Jimenez, J.; Utrilla, P.M. Free radicals scavenger and antihepatotoxic activity of Rosmarinus. Planta Med., 1993, 59, 312-314.
[40]
Yazdi, H.B.; Hojati, V.; Shiravi, A.; Hosseinian, S.; Vaezi, G.; Hadjzadeh, M.A.R. Liver dysfunction and oxidative stress in streptozotocin-induced diabetic rats: Protective role of artemisia turanica. J. Pharmacopuncture, 2019, 22(2), 109-114.
[http://dx.doi.org/10.3831/KPI.2019.22.014] [PMID: 31338251]
[41]
Giacco, F.; Brownlee, M. Oxidative stress and diabetic complications. Circ. Res., 2010, 107(9), 1058-1070.
[http://dx.doi.org/10.1161/CIRCRESAHA.110.223545] [PMID: 21030723]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy