VOLATILE ANTIDIABETIC PROPERTIES OF PIPER NIGRUM L. ETHANOL EXTRACT (ORIGINAL AND PLANT STEM CELL): NETWORK PHARMACOLOGY STUDY AND ANTIOXIDANT ACTIVITY
DOI:
https://doi.org/10.22159/ajpcr.2025v18i7.55496Keywords:
Callus, Black pepper, Diabetes mellitus, VolatileAbstract
Objectives: This study aims to identify and compare the active chemical components in the ethanol extracts of Piper nigrum L. (black pepper) plant and its callus, and to investigate their potential roles in treating diabetes mellitus (DM) through protein–protein interaction (PPI) analysis.
Methods: Ethanol extracts were prepared from both the original black pepper plant and its callus. Chemical analysis identified key active substances, including piperine and β-D-glucopyranoside, using retention times (RT). PPI investigations were conducted to determine the interactions involved in diabetes management. The antioxidant capacities of the extracts were assessed using IC50 values, and the biological processes and molecular functions related to diabetes treatment were evaluated.
Results: Both the original plant and callus extracts contained active substances such as piperine (37.715%, RT: 28.1967) and β-D-glucopyranoside (54.272%, RT: 16.5768). The primary biological processes identified were the P450 epoxygenase pathway and glycogen production. In addition, the organic acid metabolic process and nucleosome core were implicated in the management of DM by the extracts. The main molecular functions predicted were p53 binding and cyclin. The antioxidant capacities of the extracts were moderate for the callus extract (IC50: 129.92±0.83) and poor for the original plant extract (IC50: 156.69±1.36).
Conclusion: The study reveals that the ethanol extracts from the black pepper callus and the original plant possess distinct chemical profiles and mechanisms in treating DM. The callus extract demonstrates a more favorable antioxidant capacity compared to the original plant extract. Both extracts engage in similar biological processes but exhibit differences in their chemical composition and potential therapeutic pathways for diabetes management.
Downloads
References
Moodley K, Joseph K, Naidoo Y, Islam S, Mackraj I. Antioxidant, antidiabetic and hypolipidemic effects of Tulbaghia violacea harv. (Wild garlic) rhizome methanolic extract in a diabetic rat model. BMC Complement Altern Med. 2015;15:408. doi: 10.1186/s12906-015- 0932-9, PMID 26577219
Chen SC, Tseng CH. Dyslipidemia, kidney disease, and cardiovascular disease in diabetic patients. Rev Diabet Stud. 2013;10(2-3):88-100. doi: 10.1900/RDS.2013.10.88, PMID 24380085
He JH, Chen LX, Li H. Progress in the discovery of naturally occurring anti-diabetic drugs and in the identification of their molecular targets. Fitoterapia. 2019;134:270-89. doi: 10.1016/j.fitote.2019.02.033, PMID 30840917
Balbaa M, El-Zeftawy M, Abdulmalek SA. Therapeutic screening of herbal remedies for the management of diabetes. Molecules. 2021;26(22):6836. doi: 10.3390/molecules26226836, PMID 34833928
Tereshchuk L, Starovoytova K, Babich O, Dyshlyuk L, Sergeeva I, Pavsky V, et al. Sea buckthorn and rosehip oils with chokeberry extract to prevent hypercholesterolemia in mice caused by a high-fat diet in vivo. Nutrients. 2020;12(10):2941. doi: 10.3390/nu12102941, PMID 32992796
Gou GH, Liu L, Abdubakiev S, Xin XL, Akber Aisa H, Li J. Anti-diabetic effects and molecular mechanisms of amide alkaloids from Piper longum based on network pharmacology integrated with cellular assays. Chem Biodivers. 2023;20(1):e202200904. doi: 10.1002/ cbdv.202200904, PMID 36469428
Kharbanda C, Alam MS, Hamid H, Javed K, Bano S, Ali Y, et al. Novel piperine derivatives with antidiabetic effect as PPAR-γ agonists. Chem Biol Drug Des. 2016;88(3):354-62. doi: 10.1111/cbdd.12760, PMID 27037532
Khaliq T, Sarfraz M, Ashraf MA. Recent progress for the utilization of Curcuma longa, Piper nigrum and Phoenix dactylifera seeds against type 2 diabetes. West Indian Med J. 2015;64(5):527-32. doi: 10.7727/ wimj.2016.176, PMID 27399905
Kazmierski Ł, Roszkowski S. Plant stem cells culture - a new tool for skin protection and regeneration. Med Res J. 2019;4(1):52-7. doi: 10.5603/MRJ.a2018.0030
Naseem M, Dandekar T. Plant stem cells methods and protocols; 2020. In: Methods in Molecular Biology. United States: Humana Press; 2094. doi: 10.1007/978-1-0716-0183-9
Sena G. Stem cells and regeneration in plants. Nephron Exp Nephrol. 2014;126(2):35. doi: 10.1159/000360658, PMID 24854637
Abdulhafiz F, Mohammed A, Kayat F, Bhaskar M, Hamzah Z, Podapati SK, et al. Xanthine oxidase inhibitory activity, chemical composition, antioxidant properties and GC-MS analysis of keladi candik (Alocasia longiloba Miq). Molecules. 2020;25(11):2658. doi: 10.3390/molecules25112658, PMID 32521624
Ho YL, Huang SS, Deng JS, Lin YH, Chang YS, Huang GJ. In vitro antioxidant properties and total phenolic contents of wetland medicinal plants in Taiwan. Bot Stud. 2012;53:55-66.
Subasinghe S, Swamathilaka DB, Fernando KM. In vitro propagation of black pepper (Piper nigrum). In: Proceedings of the Forestry and Environmental Symposium; 27–28 February 2004; Sri Lanka. Issue: Eco-friendly Approaches Towards Sustainable Development; Section: Forest and Natural Resource Management. Sri Lanka: University of Sri Jayewardenepura; 2004. doi: 10.31357/fesympo.v0i0.1530
Hussain A, Naz S, Nazir H, Shinwari ZK. Tissue culture of black pepper (Piper nigrum L.) in Pakistan. Pak J Bot. 2011;43:1069-78.
Ikeuchi M, Sugimoto K, Iwase A. Plant callus: Mechanisms of induction and repression. Plant Cell. 2013;25(9):3159-73. doi: 10.1105/ tpc.113.116053, PMID 24076977
Thamkaew G, Sjöholm I, Galindo FG. A review of drying methods for improving the quality of dried herbs. Crit Rev Food Sci Nutr. 2021;61(11):1763-86. doi: 10.1080/10408398.2020.1765309, PMID 32423234
BPOM. Badan pengawas obat dan makanan republik Indonesia nomor 32 tahun 2019 tentang persyaratan keamanan dan mutu obat tradisional. Bpom RI. 2019;11:1-16.
Hidayat R, Wulandari P. Methods of extraction: Maceration, percolation and decoction. Eu Herb Indones. 2021;2(1):68-74. doi: 10.37275/ehi. v2i1.15
Azam S, Park JY, Kim IS, Choi DK. Piperine and its metabolite’s pharmacology in neurodegenerative and neurological diseases. Biomedicines. 2022;10(1):154. doi: 10.3390/biomedicines10010154, PMID 35052833
Sireen AA, Anbumalarmathi J. A comparative study between plant and callus extracts of Abutilon indicum (L.) Sweet: Antioxidant, antibacterial, antidiabetic and anti-proliferative activity. Int J Biochem Res Rev. 2020;29:13-24. doi: 10.9734/ijbcrr/2020/v29i930220
Xu X, Li R, Chen G, Hoopes SL, Zeldin DC, Wang DW. The role of cytochrome P450 epoxygenases, soluble epoxide hydrolase, and epoxyeicosatrienoic acids in metabolic diseases. Adv Nutr. 2016;7(6):1122-8. doi: 10.3945/an.116.012245, PMID 28140329
Wang L, Li J, Di LJ. Glycogen synthesis and beyond, a comprehensive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases. Med Res Rev. 2022;42(2):946-82. doi: 10.1002/med.21867, PMID 34729791
Mangaki A, Malviya N. Synthesis, characterization and biological evaluation of glycogen synthase kinase-3β inhibitors as antidiabetic agents. Int J Pharm Qual Assur. 2023;14(2):330-3. doi: 10.25258/ ijpqa.14.2.15
Marunaka Y. The proposal of molecular mechanisms of weak organic acids intake-induced improvement of insulin resistance in diabetes mellitus via elevation of interstitial fluid pH. Int J Mol Sci. 2018;19(10):3244. doi: 10.3390/ijms19103244, PMID 30347717
Takesue H, Hirota T, Tachimura M, Tokashiki A, Ieiri I. Nucleosome positioning and gene regulation of the SGLT2 gene in the renal proximal tubular epithelial cells. Mol Pharmacol. 2018;94(3):953-62. doi: 10.1124/mol.118.111807, PMID 29959222
Kung CP, Murphy ME. The role of the p53 tumor suppressor in metabolism and diabetes. J Endocrinol. 2016;231(2):R61-75. doi: 10.1530/JOE-16-0324, PMID 27613337
Gu J, Wang S, Guo H, Tan Y, Liang Y, Feng A, et al. Inhibition of p53 prevents diabetic cardiomyopathy by preventing early-stage apoptosis and cell senescence, reduced glycolysis, and impaired angiogenesis. Cell Death Dis. 2018;9(2):82. doi: 10.1038/s41419-017-0093-5, PMID 29362483
Bhalla K, Liu WJ, Thompson K, Anders L, Devarakonda S, Dewi R, et al. Cyclin D1 represses gluconeogenesis via inhibition of the transcriptional coactivator PGC1α. Diabetes. 2014;63(10):3266-78. doi: 10.2337/db13-1283, PMID 24947365
Saavedra-Ávila NA, Sengupta U, Sánchez B, Sala E, Haba L, Stratmann T, et al. Cyclin D3 promotes pancreatic β-cell fitness and viability in a cell cycle-independent manner and is targeted in autoimmune diabetes. Proc Natl Acad Sci U S A. 2014;111(33):E3405- 14. doi: 10.1073/pnas.1323236111, PMID 25092329
Akpoveso OP, Ubah EE, Obasanmi G. Antioxidant phytochemicals as potential therapy for diabetic complications. Antioxidants (Basel). 2023;12(1):123. doi: 10.3390/antiox12010123, PMID 36670985
Molyneux P. The use of the stable free radical diphenylpicryl-hydrazyl (DPPH) for estimating antioxidant activity. Songklanakarin J Sci Technol. 2004;26:211-9.
Ranade R, Joshi N, Kudale S. Comparative secondary metabolite expression in callus cultures and mother plant in Barleria prionitis L. Plant Cell Tiss Organ Cult. 2023;155(3):653-63. doi: 10.1007/s11240- 023-02585-5
Published
How to Cite
Issue
Section
Copyright (c) 2025 Risha Fillah Fithria

This work is licensed under a Creative Commons Attribution 4.0 International License.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.