Effects of Astragaloside IV and Formononetin on Oxidative Stress and Mitochondrial Biogenesis in Hepatocytes

Tran, Quoc-Anh; Tran, Grant Van; Velic, Sanel; Xiong, Hou-Mai; Kaur, Jaspreet; Moosavi, Zuhurr; Nguyen, Phuong; Duong, Nhi; Luu, Vy Tran; Singh, Gurjot; Bui, Tram; Rose, Melanie; Ho, Linh

doi:10.3390/ijms26020774

Open AccessArticle

Effects of Astragaloside IV and Formononetin on Oxidative Stress and Mitochondrial Biogenesis in Hepatocytes

by

Quoc-Anh Tran

,

Grant Van Tran

^†,

Sanel Velic

^†,

Hou-Mai Xiong

,

Jaspreet Kaur

,

Zuhurr Moosavi

,

Phuong Nguyen

,

Nhi Duong

,

Vy Tran Luu

,

Gurjot Singh

,

Tram Bui

,

Melanie Rose

and

Linh Ho

^*

College of Pharmacy, California Northstate University, Elk Grove, CA 95757, USA

^*

Author to whom correspondence should be addressed.

^†

Grant Van Tran and Sanel Velic contributed equally to this work.

Int. J. Mol. Sci. 2025, 26(2), 774; https://doi.org/10.3390/ijms26020774

Submission received: 6 December 2024 / Revised: 7 January 2025 / Accepted: 11 January 2025 / Published: 17 January 2025

(This article belongs to the Special Issue The Role of Epigenetics in Genome Maintenance and Its Relationship to Organismal Aging and Age-Related Diseases)

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Abstract

Over-accumulation of reactive oxygen species (ROS) causes hepatocyte dysfunction and apoptosis that might lead to the progression of liver damage. Sirtuin-3 (SIRT3), the main NAD+-dependent deacetylase located in mitochondria, has a critical role in regulation of mitochondrial function and ROS production as well as in the mitochondrial antioxidant mechanism. This study explores the roles of astragaloside IV (AST-IV) and formononetin (FMR) in connection with SIRT3 for potential antioxidative effects. It was shown that the condition of combined pre- and post-treatment with AST-IV or FMR at all concentrations statistically increased and rescued cell proliferation. ROS levels were not affected by pre-or post-treatment individually with AST-IV or pre-treatment with FMR; however, post-treatment with FMR resulted in significant increases in ROS in all groups. Significant decreases in ROS levels were seen when pre- and post-treatment with AST-IV were combined at 5 and 10 μM, or FMR at 5 and 20 μM. In the condition of combined pre- and post-treatment with 10 μM AST-IV, there was a significant increase in SOD activity, and the transcriptional levels of Sod2, Cat, and GPX1 in all treatment groups, which is indicative of reactive oxygen species detoxification. Furthermore, AST-IV and FMR activated PGC-1α and AMPK as well as SIRT3 expression in AML12 hepatocytes exposed to t-BHP-induced oxidative stress, especially at high concentrations of FMR. This study presents a novel mechanism whereby AST-IV and FMR yield an antioxidant effect through induction of SIRT3 protein expression and activation of an antioxidant mechanism as well as mitochondrial biogenesis and mitochondrial content and potential. The findings suggest these agents can be used as SIRT3 modulators in treating oxidative-injury hepatocytes.

Keywords: astragaloside; formononetin; SIRT3 modulators; oxidative stress; oxidative injury; tert-butyl hydrogen peroxide (t-BHP); mitochondrial sirtuins; SIRT3

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MDPI and ACS Style

Tran, Q.-A.; Tran, G.V.; Velic, S.; Xiong, H.-M.; Kaur, J.; Moosavi, Z.; Nguyen, P.; Duong, N.; Luu, V.T.; Singh, G.; et al. Effects of Astragaloside IV and Formononetin on Oxidative Stress and Mitochondrial Biogenesis in Hepatocytes. Int. J. Mol. Sci. 2025, 26, 774. https://doi.org/10.3390/ijms26020774

AMA Style

Tran Q-A, Tran GV, Velic S, Xiong H-M, Kaur J, Moosavi Z, Nguyen P, Duong N, Luu VT, Singh G, et al. Effects of Astragaloside IV and Formononetin on Oxidative Stress and Mitochondrial Biogenesis in Hepatocytes. International Journal of Molecular Sciences. 2025; 26(2):774. https://doi.org/10.3390/ijms26020774

Chicago/Turabian Style

Tran, Quoc-Anh, Grant Van Tran, Sanel Velic, Hou-Mai Xiong, Jaspreet Kaur, Zuhurr Moosavi, Phuong Nguyen, Nhi Duong, Vy Tran Luu, Gurjot Singh, and et al. 2025. "Effects of Astragaloside IV and Formononetin on Oxidative Stress and Mitochondrial Biogenesis in Hepatocytes" International Journal of Molecular Sciences 26, no. 2: 774. https://doi.org/10.3390/ijms26020774

APA Style

Tran, Q.-A., Tran, G. V., Velic, S., Xiong, H.-M., Kaur, J., Moosavi, Z., Nguyen, P., Duong, N., Luu, V. T., Singh, G., Bui, T., Rose, M., & Ho, L. (2025). Effects of Astragaloside IV and Formononetin on Oxidative Stress and Mitochondrial Biogenesis in Hepatocytes. International Journal of Molecular Sciences, 26(2), 774. https://doi.org/10.3390/ijms26020774

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Effects of Astragaloside IV and Formononetin on Oxidative Stress and Mitochondrial Biogenesis in Hepatocytes

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