IDENTIFYING THE POTENTIAL OF Saurauia vulcani Korth. LEAVES ON BLOOD GLUCOSE LEVEL, HISTOPATHOLOGY OF PANCREATIC AND SPLEEN IN RATS (Rattus norvegicus) INDUCED ALLOXAN – IN VIVO AND IN SILICO APPROACH

Erlintan Sinaga, Uswatun Hasanah, Feimmy Ruth Pratiwi Sipahutar, Hudson Sidabutar, Melati Nugrahalia Sipahutar

Abstract


Insulin resistance related to pancreatic islet and spleen was one of incidence for diabetes mellitus disease. Our study determined the potential antidiabetic of Pirdot leaves (Saurauia vulcani, Korth.) (EEP) through in vivo and in silico approach. The effect of Pirdot on blood glucose level and histopathological pancreatic and spleen was analyzed by in vivo. Thirty male Wistar rats were divided into five groups as follows. Group KN served as negative control and was orally given distilled water; group KP were only 5.04 mg/ kg alloxan administered; group P1 were administered 16.5 mg/kg EEP and 5.04 mg/kg alloxan; group P2 were administered 33 mg/kg EEP and 5.04 mg/kg alloxan; group P3 rats 66 mg/kg EEP and 5.04 mg/kg alloxan. A single dose of alloxan was given in rats diabetic at KP, P1, P2, and P3 group treatment. Furthermore, the protein-protein interaction (PPI) and molecular docking were used to predict the interaction between the crossed genes in diabetes mellitus (DM) with 6 active compounds of Pirdot through in silico approach. The results indicated that Saurauia vulcani significantly decreased blood glucose and improved the histopathological alteration of pancreatic islet and spleen in alloxan induced treated diabetic rats. Moreover, the network pharmacology demonstrated ten hub genes and three genes target such as GANC (α-glucosidase), DPP4, and PTPN1 (tyrosine phosphatase protein) contributed in DM signaling pathway. Finally, the molecular docking study showed that the bioactive compounds Pirdot have a good binding affinity to the active site of PTP1B and α-glucosidase protein when compared to acarbose as a control compound


Keywords


Ekstrak etanol Saurauia, indeks organ, hati, inflamasi

References


Ang, L., Dillon, B., Mizokami-Stout, K. & Pop-Busui, R. Cardiovascular autonomic neuropathy: A silent killer with long reach. Auton. Neurosci. 225, 102646 (2020).

Eissa, L. D., Ghobashy, W. A. & El-Azab, M. F. Inhibition of thioredoxin-interacting protein and inflammasome assembly using verapamil mitigates diabetic retinopathy and pancreatic injury. Eur. J. Pharmacol. 901, 174061 (2021).

Migdalis, I. N. et al. The prevalence of diabetic chronic kidney disease in adult Greek subjects with type 2 diabetes mellitus: A series from hospital-based diabetes clinics. Diabetes Res. Clin. Pract. 166, 108243 (2020).

Bolat, M. S., Cinar, O., Akdeniz, E. & Aşcı, R. Low dose daily versus on-demand high dose tadalafil in diabetic patients with erectile and ejaculatory dysfunction. Int. J. Impot. Res. 30, 102–107 (2018).

Zhu, P. et al. AGEs-induced MMP-9 activation mediated by Notch1 signaling is involved in impaired wound healing in diabetic rats. Diabetes Res. Clin. Pract. 186, 109831 (2022).

Murugesan, A., Yadav, S. K. R. & Dixit, A. Anti-hyperglycemic activity of HPLC-fractionated Momordica charantia seed extract enriched in a novel napin-like protein in experimental diabetic rats and its validation with recombinant napin-like protein. Curr. Res. Biotechnol. 4, 179–189 (2022).

Moyer, E. D., Lehman, E. B., Bolton, M. D., Goldstein, J. & Pichardo-Lowden, A. R. Lack of recognition and documentation of stress hyperglycemia is a disruptor of optimal continuity of care. Sci. Rep. 11, 11476 (2021).

Ojo, O. A. et al. Antidiabetic activity of avocado seeds (Persea americana Mill.) in diabetic rats via activation of PI3K/AKT signaling pathway. Sci. Rep. 12, 2919 (2022).

Zhou, D. Y., Mou, X., Liu, K., Liu, W. H. & Xu, Y. Q. In silico prediction and validation of potential therapeutic genes in pancreatic β-cells associated with type 2 diabetes. Exp. Ther. Med. 20, (2020).

Figueiredo, A., Leal, E. C. & Carvalho, E. Protein tyrosine phosphatase 1B inhibition as a potential therapeutic target for chronic wounds in diabetes. Pharmacol. Res. 159, 104977 (2020).

Wang, Y., Hu, B., Feng, S., Wang, J. & Zhang, F. Target recognition and network pharmacology for revealing anti-diabetes mechanisms of natural product. J. Comput. Sci. 45, 101186 (2020).

Iraji, A. et al. Cyanoacetohydrazide linked to 1,2,3-triazole derivatives: a new class of α-glucosidase inhibitors. Sci. Rep. 12, 8647 (2022).

Ranjan, A. et al. Characterization and evaluation of mycosterol secreted from endophytic strain of Gymnema sylvestre for inhibition of α-glucosidase activity. Sci. Rep. 9, 17302 (2019).

Proença, C. et al. α-Glucosidase inhibition by flavonoids: an in vitro and in silico structure–activity relationship study. J. Enzyme Inhib. Med. Chem. 32, 1216–1228 (2017).

Tian, J.-L. et al. Bioactive flavonoids from Rubus corchorifolius inhibit α-glucosidase and α-amylase to improve postprandial hyperglycemia. Food Chem. 341, 128149 (2021).

Zhao, Z. et al. Reveals of quercetin’s therapeutic effects on oral lichen planus based on network pharmacology approach and experimental validation. Sci. Rep. 12, 1162 (2022).

Bai, X. et al. Network pharmacology integrated molecular docking reveals the bioactive components and potential targets of Morinda officinalis–Lycium barbarum coupled-herbs against oligoasthenozoospermia. Sci. Rep. 11, 2220 (2021).

Li, F. et al. A network pharmacology approach to reveal the protective mechanism of Salvia miltiorrhiza-Dalbergia odorifera coupled-herbs on coronary heart disease. Sci. Rep. 9, 19343 (2019).

Situmorang, R. O. & Sunandar, A. D. Pirdot (Saurauia bracteosa DC) Leaf Processing Technique for Making Herbal Tea. IOP Conf. Ser. Earth Environ. Sci. 359, (2019).

Konappa, N. et al. GC–MS analysis of phytoconstituents from Amomum nilgiricum and molecular docking interactions of bioactive serverogenin acetate with target proteins. Sci. Rep. 10, 16438 (2020).

Sitorus, P., Rosidah & Satria, D. Hypoglycemic activity of ethanolic extract of saurauia vulcani korth. Leaves. Asian J. Pharm. Clin. Res. 11, 35–36 (2018).

Sitorus, P. Characterization simplisia and ethanolic extract of pirdot (Saurauia Vulcani, Korth) leaves and study of antidiabetic effect in alloxan induced diabetic mice. Int. J. ChemTech Res. 8, 789–794 (2015).

Hutahaean, S., Tanjung, M., Sari, D. P. & Ningsih, V. E. Antihyperglycemic and antihyperlipidemic effects of pirdot (saurauia vulcani korth.) leaves extract in mice. IOP Conf. Ser. Earth Environ. Sci. 130, (2018).

Pasaribu, G., Waluyo, T. K. & Winarni, I. Phytochemical content, toxicity and antioxidant activities of native medicinal plants from North Sumatra. IOP Conf. Ser. Earth Environ. Sci. 591, (2020).

Lovena, T. N., Harahap, U., Sitorus, P. & Satria, D. Antioxidant activity and α-glucosidase inhibition effect of water extract Saurauia vulcani Korth leaves. J. Innov. Pharm. Biol. Sci. 5, 47–51 (2018).

Sinaga, E., Ilyas, S., Hutahaean, S. & Sitorus, P. Immunostimulatory Activity from Pirdot Leaves Ethanolic Extract (Saurauia vulcani Korth.) in Rats (Rattus norvegicus). IOP Conf. Ser. Earth Environ. Sci. 305, 12082 (2019).

Amah, C. C. et al. Ethyl acetate fraction of Fagara zanthoxyloides root-bark possess antidiabetic property against alloxan-induced diabetes and its complications in Wistar rat model. J. Ethnopharmacol. 115259 (2022) doi:https://doi.org/10.1016/j.jep.2022.115259.

Sajid, M. et al. Antidiabetic and antioxidant potential of Alnus nitida leaves in alloxan induced diabetic rats. J. Ethnopharmacol. 251, 112544 (2020).

Sarker, S. Z. T. R. M. R., Rahmat, A., Alkahtani, S. A. & Othman, F. The effect of pomegranate fresh juice versus pomegranate seed powder on metabolic indices, lipid profile, inflammatory biomarkers, and the histopathology of pancreatic islets of Langerhans in streptozotocin-nicotinamide induced type 2 diabetic Sprague-Daw. BMC Complement. Altern. Med. 17, (2017).

Gonzalez, A. A., Hamele-Bena, D., Wood, T., Valladares-Silva, S. & Wasserman, P. G. Pneumocystis jirovecii immunostain versus Gomori/Grocott methenamine silver stain of bronchoalveolar lavage in cell blocks: an institutional experience. J. Am. Soc. Cytopathol. 6, 242–247 (2017).

Xiao, G. et al. Network pharmacology analysis and experimental validation to explore the mechanism of Bushao Tiaozhi capsule (BSTZC) on hyperlipidemia. Sci. Rep. 12, 6992 (2022).

An, W. et al. Mechanisms of Rhizoma Coptidis against type 2 diabetes mellitus explored by network pharmacology combined with molecular docking and experimental validation. Sci. Rep. 11, 20849 (2021).

Younis, I. Y. et al. Metabolomics-based profiling of 4 avocado varieties using HPLC–MS/MS and GC/MS and evaluation of their antidiabetic activity. Sci. Rep. 12, 4966 (2022).

Swilam, N., Nawwar, M. A. M., Radwan, R. A. & Mostafa, E. S. Antidiabetic Activity and In Silico Molecular Docking of Polyphenols from Ammannia baccifera L. subsp. Aegyptiaca (Willd.) Koehne Waste: Structure Elucidation of Undescribed Acylated Flavonol Diglucoside. Plants (Basel, Switzerland) 11, (2022).

Jaradat, N. et al. Antidiabetic, antioxidant, and anti-obesity effects of phenylthio-ethyl benzoate derivatives, and molecular docking study regarding α-amylase enzyme. Sci. Rep. 12, 3108 (2022).

Riaz, M. A. et al. Assessment of metals induced histopathological and gene expression changes in different organs of non-diabetic and diabetic rats. Sci. Rep. 10, 5897 (2020).

Shan, C., Ji, X., Wu, Z. & Zhao, J. Network pharmacology combined with GEO database identifying the mechanisms and molecular targets of Polygoni Cuspidati Rhizoma on Peri-implants. Sci. Rep. 12, 8227 (2022).

Balaich, J. et al. The human microbiome encodes resistance to the antidiabetic drug acarbose. Nature 600, 110–115 (2021).

Farrehi, C., Pazzi, C. & Stillman, M. A case of postprandial hypotension in an individual with cervical spinal cord injury: treatment with acarbose. Spinal Cord Ser. Cases 5, 75 (2019).

Bittenglova, K., Habart, D., Saudek, F. & Koblas, T. The Potential of Pancreatic Organoids for Diabetes Research and Therapy. Islets 13, 85–105 (2021).

Yang, C. et al. Hyperglycemia-triggered ATF6-CHOP pathway aggravates acute inflammatory liver injury by β-catenin signaling. Cell Death Discov. 8, 115 (2022).

Obi, P. E., Ezeorah, C. C., Odoh, U. E. & Offiah, R. O. Effect of ethanol leaf extract of Clerodendrum splendens (G. Don) (Verbenaceae) on some biochemical parameters of Alloxan-induced diabetic Wistar rats. Phytomedicine Plus 2, 100147 (2022).

Abdulkareem, A. O., Igunnu, A., Ala, A. A. & Olatunji, L. A. Leaf extract of Morinda lucida improves pancreatic beta-cell function in alloxan-induced diabetic rats. Egypt. J. Basic Appl. Sci. 6, 73–81 (2019).

Sanad, F. A.-A., Ahmed, S. F. & El-Tantawy, W. H. Antidiabetic and hypolipidemic potentials of Solidago virgaurea extract in alloxan-induced diabetes type 1. Arch. Physiol. Biochem. 1–8 (2020) doi:10.1080/13813455.2020.1722705.

Anastasia, G., Sitorus, P. & Satria, D. Wound Healing Activity of Saurauia vulcani Korth Aqueous Leaves Extract Evaluation on Excision Wound in Hyperglycemia Rats. J. Innov. Pharm. Biol. Sci. 5, 52–57 (2018).

Sinaga, E., Ilyas, S., Hutahaean, S. & Sitorus, P. Hepatoprotective Activity of Pirdot Leaves (Saurauia vulcani Korth) Ethanol Extract in Laboratory Rats (Rattus norvegicus) and Characterization of Bioactive Compounds Using a Molecular Docking Approach. Open Access Maced. J. Med. Sci. 9, 1265–1270 (2021).

Shi, Y. & Meng, X. Insulin Aspart Combined with Exercise Therapy in Spleen Deficiency Type Gestational Diabetes Mellitus: The Effect on Disease Control and Pregnancy Outcomes. Evid. - Based Complement. Altern. Med. 2022, (2022).

Wigger, L. et al. Multi-omics profiling of living human pancreatic islet donors reveals heterogeneous beta cell trajectories towards type 2 diabetes. Nat. Metab. 3, 1017–1031 (2021).

Xu, M. et al. Elucidation of the Mechanisms and Molecular Targets of Sanhuang Xiexin Decoction for Type 2 Diabetes Mellitus Based on Network Pharmacology. Biomed Res. Int. 2020, (2020).

Chen, M. et al. CTNNB1/β-catenin dysfunction contributes to adiposity by regulating the cross-talk of mature adipocytes and preadipocytes. Sci. Adv. 6, eaax9605–eaax9605 (2020).

Zhu, K. et al. Kindlin-2 modulates MafA and β-catenin expression to regulate β-cell function and mass in mice. Nat. Commun. 11, 484 (2020).

Chang, H.-Y. et al. Selective serotonin reuptake inhibitor, fluoxetine, impairs E-cadherin-mediated cell adhesion and alters calcium homeostasis in pancreatic beta cells. Sci. Rep. 7, 3515 (2017).

Talakatta, G. et al. Diabetes induces fibrotic changes in the lung through the activation of TGF-β signaling pathways. Sci. Rep. 8, 11920 (2018).

Noor, F. et al. Integrating Network Pharmacology and Molecular Docking Approaches to Decipher the Multi-Target Pharmacological Mechanism of Abrus precatorius L. Acting on Diabetes. Pharmaceuticals 15, 414 (2022).

Khanal, P. & Patil, B. M. α-Glucosidase inhibitors from Duranta repens modulate p53 signaling pathway in diabetes mellitus. Adv. Tradit. Med. 20, 427–438 (2020).

Xu, Z. et al. METTL14-regulated PI3K/Akt signaling pathway via PTEN affects HDAC5-mediated epithelial–mesenchymal transition of renal tubular cells in diabetic kidney disease. Cell Death Dis. 12, 32 (2021).

Just, P.-A. et al. Lkb1 suppresses amino acid-driven gluconeogenesis in the liver. Nat. Commun. 11, 6127 (2020).

Wen, X. et al. Signaling pathways in obesity: mechanisms and therapeutic interventions. Signal Transduct. Target. Ther. 7, 298 (2022).

Gardner, G. & Fraker, C. A. Natural Killer Cells as Key Mediators in Type I Diabetes Immunopathology. Front. Immunol. 12, 722979 (2021).

Zhou, Q. et al. Phenylalanine impairs insulin signaling and inhibits glucose uptake through modification of IRβ. Nat. Commun. 13, 4291 (2022).

Zhou, L. et al. Induced regulatory T cells suppress Tc1 cells through TGF-β signaling to ameliorate STZ-induced type 1 diabetes mellitus. Cell. Mol. Immunol. 18, 698–710 (2021).

Veluthakal, R. & Thurmond, D. C. Emerging Roles of Small GTPases in Islet β-Cell Function. Cells vol. 10 (2021).

Vanweert, F., Schrauwen, P. & Phielix, E. Role of branched-chain amino acid metabolism in the pathogenesis of obesity and type 2 diabetes-related metabolic disturbances BCAA metabolism in type 2 diabetes. Nutr. Diabetes 12, 35 (2022).

Kwon, H.-K. et al. A cell-penetrating peptide blocks Toll-like receptor-mediated downstream signaling and ameliorates autoimmune and inflammatory diseases in mice. Exp. Mol. Med. 51, 1–19 (2019).




DOI: https://doi.org/10.24114/jbio.v9i2.53242

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JBIO : Jurnal Biosains (The Journal of Biosciences), Program Studi Biologi, Fakultas Matematika dan Ilmu Pengetahuan Alam, Universitas Negeri Medan. ISSN 2443-1230 (print) dan ISSN 2460-6804 (online)

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