E-ISSN 2218-6050 | ISSN 2226-4485
 

Research Article


Neuroprotection effect of bovine umbilical mesenchymal stem cell-conditioned medium on the rat model of Alzheimer’s disease mediated by upregulation of BDNF and NGF and downregulation of TNF-α and IL-1β

Hevi Wihadmadyatami, Muhammad Ali Zulfikar, Herawati Herawati, Srikanth Karnati, Golda Rani Saragih, Dinda Aliffia, Dyah A.o.a. Pratama, Nurrahmi Handayani, Ulayatul Kustiati, Dewi Ratih Tirtosari, Yudy Tjahjono.


Abstract
Background:
Neurodegenerative diseases (NDD) are distinguished by impairment and depletion of nerve cells; one of the most common NDDs is Alzheimer's Disease (AD), which can appear in early onset or late onset. In recent years, the secretome or conditioned medium of mesenchymal stem cells provides new hope for improving conditions and preventing AD. One of the secretomes is bovine umbilical mesenchymal stem cells conditioned medium (BUMSC-CM), where BUMSC is predicted to promote neuronal proliferation potentially.

Aim:
This study analyzes the therapeutic efficiency of conditioned medium or secretome produced from BUMSC-CM in treating neurodegeneration in animal models of AD.

Methods:
Five groups consisting of twenty-five male rats were assigned: untreated (Group A, n=5), positive control group given normal saline 1 ml/100 g BW (Group B, n=5), AD rats model followed by Donepezil treatment (Group C, n=5), AD rats model with BUMSC-CM 0.2 ml/kg BW post-TMT induction (Group D, n=5), and AD rats model with BUMSC-CM 0.5 ml/kg BW post-TMT induction (Group E, n=5). Brain samples were analyzed for neuronal density using cresyl violet staining. The expression and activity of BDNF were analyzed by ELISA, in addition IL-1β, TNF-α, and NGF were analyzed by qPCR. Interactions between the main substances of BUMSC-CM and beta-amyloid protein were visualized using in silico molecular docking.

Results:
Our result demonstrated that BUMSC-CM with the dosage of 0,5 ml/kg BW significantly increased BDNF concentration. We also found that BUMSC-CM with dosage 0.2 ml/kg BW and 0.5 ml/kg BW down-regulated IL-1β and TNF-α and upregulated NGF expression. Additionally, the number of neurons in AD rats post-treated with BUMSC-CM was significantly increasing. Furthermore, the amino acids in BUMSC-CM, including isoleucine, leucine, and valine, bind to amyloid beta protein via interactions that are hydrophobic and hydrogen-bonded.

Conclusion:
In this study, the neuroprotective potential of BUMSC-CM was demonstrated by its ability to upregulate BDNF and NGF while downregulating IL-1β and TNF-α. Additionally, BUMSC-CM showed potential to promote neuron proliferation in the hippocampus regions of a rat AD model. The main constituents in BUMSC-CM adhere to amyloid beta protein, hence diminishing the likelihood of neurodegenerative disorders, specifically AD.

Key words: Alzheimer’s disease, BUMSC-CM, Rat Model, TNF-α, IL-1β


 
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How to Cite this Article
Pubmed Style

Wihadmadyatami H, Zulfikar MA, Herawati H, Karnati S, Saragih GR, Aliffia D, Pratama DA, Handayani N, Kustiati U, Tirtosari DR, Tjahjono Y. Neuroprotection effect of bovine umbilical mesenchymal stem cell-conditioned medium on the rat model of Alzheimer’s disease mediated by upregulation of BDNF and NGF and downregulation of TNF-α and IL-1β. Open Vet J. 2025; 15(1): 151-161. doi:10.5455/OVJ.2025.v15.i1.14


Web Style

Wihadmadyatami H, Zulfikar MA, Herawati H, Karnati S, Saragih GR, Aliffia D, Pratama DA, Handayani N, Kustiati U, Tirtosari DR, Tjahjono Y. Neuroprotection effect of bovine umbilical mesenchymal stem cell-conditioned medium on the rat model of Alzheimer’s disease mediated by upregulation of BDNF and NGF and downregulation of TNF-α and IL-1β. https://www.openveterinaryjournal.com/?mno=213898 [Access: March 18, 2025]. doi:10.5455/OVJ.2025.v15.i1.14


AMA (American Medical Association) Style

Wihadmadyatami H, Zulfikar MA, Herawati H, Karnati S, Saragih GR, Aliffia D, Pratama DA, Handayani N, Kustiati U, Tirtosari DR, Tjahjono Y. Neuroprotection effect of bovine umbilical mesenchymal stem cell-conditioned medium on the rat model of Alzheimer’s disease mediated by upregulation of BDNF and NGF and downregulation of TNF-α and IL-1β. Open Vet J. 2025; 15(1): 151-161. doi:10.5455/OVJ.2025.v15.i1.14



Vancouver/ICMJE Style

Wihadmadyatami H, Zulfikar MA, Herawati H, Karnati S, Saragih GR, Aliffia D, Pratama DA, Handayani N, Kustiati U, Tirtosari DR, Tjahjono Y. Neuroprotection effect of bovine umbilical mesenchymal stem cell-conditioned medium on the rat model of Alzheimer’s disease mediated by upregulation of BDNF and NGF and downregulation of TNF-α and IL-1β. Open Vet J. (2025), [cited March 18, 2025]; 15(1): 151-161. doi:10.5455/OVJ.2025.v15.i1.14



Harvard Style

Wihadmadyatami, H., Zulfikar, . M. A., Herawati, . H., Karnati, . S., Saragih, . G. R., Aliffia, . D., Pratama, . D. A., Handayani, . N., Kustiati, . U., Tirtosari, . D. R. & Tjahjono, . Y. (2025) Neuroprotection effect of bovine umbilical mesenchymal stem cell-conditioned medium on the rat model of Alzheimer’s disease mediated by upregulation of BDNF and NGF and downregulation of TNF-α and IL-1β. Open Vet J, 15 (1), 151-161. doi:10.5455/OVJ.2025.v15.i1.14



Turabian Style

Wihadmadyatami, Hevi, Muhammad Ali Zulfikar, Herawati Herawati, Srikanth Karnati, Golda Rani Saragih, Dinda Aliffia, Dyah A.o.a. Pratama, Nurrahmi Handayani, Ulayatul Kustiati, Dewi Ratih Tirtosari, and Yudy Tjahjono. 2025. Neuroprotection effect of bovine umbilical mesenchymal stem cell-conditioned medium on the rat model of Alzheimer’s disease mediated by upregulation of BDNF and NGF and downregulation of TNF-α and IL-1β. Open Veterinary Journal, 15 (1), 151-161. doi:10.5455/OVJ.2025.v15.i1.14



Chicago Style

Wihadmadyatami, Hevi, Muhammad Ali Zulfikar, Herawati Herawati, Srikanth Karnati, Golda Rani Saragih, Dinda Aliffia, Dyah A.o.a. Pratama, Nurrahmi Handayani, Ulayatul Kustiati, Dewi Ratih Tirtosari, and Yudy Tjahjono. "Neuroprotection effect of bovine umbilical mesenchymal stem cell-conditioned medium on the rat model of Alzheimer’s disease mediated by upregulation of BDNF and NGF and downregulation of TNF-α and IL-1β." Open Veterinary Journal 15 (2025), 151-161. doi:10.5455/OVJ.2025.v15.i1.14



MLA (The Modern Language Association) Style

Wihadmadyatami, Hevi, Muhammad Ali Zulfikar, Herawati Herawati, Srikanth Karnati, Golda Rani Saragih, Dinda Aliffia, Dyah A.o.a. Pratama, Nurrahmi Handayani, Ulayatul Kustiati, Dewi Ratih Tirtosari, and Yudy Tjahjono. "Neuroprotection effect of bovine umbilical mesenchymal stem cell-conditioned medium on the rat model of Alzheimer’s disease mediated by upregulation of BDNF and NGF and downregulation of TNF-α and IL-1β." Open Veterinary Journal 15.1 (2025), 151-161. Print. doi:10.5455/OVJ.2025.v15.i1.14



APA (American Psychological Association) Style

Wihadmadyatami, H., Zulfikar, . M. A., Herawati, . H., Karnati, . S., Saragih, . G. R., Aliffia, . D., Pratama, . D. A., Handayani, . N., Kustiati, . U., Tirtosari, . D. R. & Tjahjono, . Y. (2025) Neuroprotection effect of bovine umbilical mesenchymal stem cell-conditioned medium on the rat model of Alzheimer’s disease mediated by upregulation of BDNF and NGF and downregulation of TNF-α and IL-1β. Open Veterinary Journal, 15 (1), 151-161. doi:10.5455/OVJ.2025.v15.i1.14