Modified Tabusen-2, a Natural Multi-Herb Bioactive Formula with Antioxidant Potential, Ameliorates Kidney–Bone Axis Disorders in Rats via the STAT3/TP53 Axis and Steroid Hormone Biosynthesis
- 1Department of Pharmacy, Inner Mongolia Medical University, Jinshan Development Zone, Hohhot 010110, China
- 2School of Pharmacy, Henan University of Chinese Medicine, No. 156 East Road, Jinshui District, Zhengzhou 450046, China
Abstract
Background/Objectives: Postmenopausal osteoporosis (PMOP) and kidney-yang deficiency (KYD) are major kidney–bone axis disorders with a growing public health burden, yet current therapies are largely single-target and fail to address the coordinated dysfunction of the renal and skeletal systems. Modified Tabusen-2 (MT-2), a multi-herb Mongolian formula whose constituent herbs contain natural bioactive compounds with reported antioxidant and anti-inflammatory activities, reportedly improves both conditions; however, the shared molecular mechanism underlying its dual efficacy remains undefined, hindering its standardization and clinical translation. Methods: We integrated untargeted metabolomics, network pharmacology, targeted LC-MS/MS-based steroid hormone quantification, and qRT-PCR in rat models of hydrocortisone-induced KYD and ovariectomy-induced PMOP treated with MT-2 at high, medium, or low doses for 8 weeks. Results: MT-2 significantly alleviated pathological phenotypes and normalized serum biomarkers in both models. Network pharmacology and metabolomics converged on steroid hormone biosynthesis as the shared core pathway, and targeted quantification confirmed that seven serum steroid hormones were significantly dysregulated (p < 0.05) and effectively reversed by MT-2. qRT-PCR further showed that STAT3 and TP53, transcriptional hubs responsive to oxidative stress and inflammatory signaling, were significantly upregulated in disease groups (p < 0.05) and downregulated after MT-2 treatment. Conclusions: These findings provide molecular evidence supporting the “kidney governing bones” theory and suggest that MT-2 acts through coordinated regulation of steroid hormone biosynthesis and the STAT3/TP53 axis, supporting MT-2 as a multi-target natural bioactive candidate for kidney–bone axis disorders.
Related
- Gut microbiota- and probiotic-derived bioactive metabolites: mechanisms, evidence, and therapeutic potential in metabolic disorders
- GPX4-Mediated Inhibition of Ferroptosis by Sodium Selenite Ameliorates Bone Metabolic Disorders in Ovariectomized Mice.
- The Impact of High-Temperature and High-Pressure Steaming Treatment on Bioactive Compounds and Antioxidant Activity in American Ginseng
- Lycium barbarum Polysaccharide Fraction Ameliorates Palmitate-Induced Insulin Signaling Impairment in HepG2 Cells: Transcriptomic Evidence for the Potential Association with the DAG-PtdOH Metabolic Axis and the AMPK/ULK1 Autophagy Pathway
- Wheat Bioactive Compounds and Human Health: A Review of Nutraceutical Potential, Molecular Mechanisms and AI-Assisted Functional Food Innovation
BibTeX
@article{wang2026modified,
title = {{Modified Tabusen-2, a Natural Multi-Herb Bioactive Formula with Antioxidant Potential, Ameliorates Kidney–Bone Axis Disorders in Rats via the STAT3/TP53 Axis and Steroid Hormone Biosynthesis}},
author = {Zhi Wang and Bi Qu and Shu Guo and Jie Liu and Yuxin Tian and Jingkun Lu and Ren Bu and Peifeng Xue and Xin Dong},
journal = {Metabolites},
year = {2026},
month = oct,
doi = {10.3390/metabo16110829},
url = {https://www.mdpi.com/2218-1989/16/11/829},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Modified Tabusen-2, a Natural Multi-Herb Bioactive Formula with Antioxidant Potential, Ameliorates Kidney–Bone Axis Disorders in Rats via the STAT3/TP53 Axis and Steroid Hormone Biosynthesis
AU - Zhi Wang
AU - Bi Qu
AU - Shu Guo
AU - Jie Liu
AU - Yuxin Tian
AU - Jingkun Lu
AU - Ren Bu
AU - Peifeng Xue
AU - Xin Dong
PY - 2026
DA - 2026/10/29
JO - Metabolites
DO - 10.3390/metabo16110829
UR - https://www.mdpi.com/2218-1989/16/11/829
AB - Background/Objectives: Postmenopausal osteoporosis (PMOP) and kidney-yang deficiency (KYD) are major kidney–bone axis disorders with a growing public health burden, yet current therapies are largely single-target and fail to address the coordinated dysfunction of the renal and skeletal systems. Modified Tabusen-2 (MT-2), a multi-herb Mongolian formula whose constituent herbs contain natural bioactive compounds with reported antioxidant and anti-inflammatory activities, reportedly improves both conditions; however, the shared molecular mechanism underlying its dual efficacy remains undefined, hindering its standardization and clinical translation. Methods: We integrated untargeted metabolomics, network pharmacology, targeted LC-MS/MS-based steroid hormone quantification, and qRT-PCR in rat models of hydrocortisone-induced KYD and ovariectomy-induced PMOP treated with MT-2 at high, medium, or low doses for 8 weeks. Results: MT-2 significantly alleviated pathological phenotypes and normalized serum biomarkers in both models. Network pharmacology and metabolomics converged on steroid hormone biosynthesis as the shared core pathway, and targeted quantification confirmed that seven serum steroid hormones were significantly dysregulated (p < 0.05) and effectively reversed by MT-2. qRT-PCR further showed that STAT3 and TP53, transcriptional hubs responsive to oxidative stress and inflammatory signaling, were significantly upregulated in disease groups (p < 0.05) and downregulated after MT-2 treatment. Conclusions: These findings provide molecular evidence supporting the “kidney governing bones” theory and suggest that MT-2 acts through coordinated regulation of steroid hormone biosynthesis and the STAT3/TP53 axis, supporting MT-2 as a multi-target natural bioactive candidate for kidney–bone axis disorders.
SN - 2218-1989
ER -