Flavonoid Compounds from Shenrong Guben Huanshao Pill alleviates senescence-associated mitochondrial dysfunction through NDUFV2 and LDHB mediated metabolic reprogramming

Xiaohui Hu; Yingxia Tian; Qianping Chen; Yanan Guo; Pengfei Ji; Yixiao Tian; Shuangxi Qian; Guolin Chai; Fangdi Hu; Rong Shen; Degui Wang

doi:10.1016/j.jpha.2026.101559

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Xiaohui Hu, Yingxia Tian, Qianping Chen, Yanan Guo, Pengfei Ji, Yixiao Tian, Shuangxi Qian, Guolin Chai, Fangdi Hu, Rong Shen, Degui Wang. Flavonoid Compounds from Shenrong Guben Huanshao Pill alleviates senescence-associated mitochondrial dysfunction through NDUFV2 and LDHB mediated metabolic reprogramming[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101559

Citation:

Xiaohui Hu, Yingxia Tian, Qianping Chen, Yanan Guo, Pengfei Ji, Yixiao Tian, Shuangxi Qian, Guolin Chai, Fangdi Hu, Rong Shen, Degui Wang. Flavonoid Compounds from Shenrong Guben Huanshao Pill alleviates senescence-associated mitochondrial dysfunction through NDUFV2 and LDHB mediated metabolic reprogramming[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101559

Citation:

Xiaohui Hu, Yingxia Tian, Qianping Chen, Yanan Guo, Pengfei Ji, Yixiao Tian, Shuangxi Qian, Guolin Chai, Fangdi Hu, Rong Shen, Degui Wang. Flavonoid Compounds from Shenrong Guben Huanshao Pill alleviates senescence-associated mitochondrial dysfunction through NDUFV2 and LDHB mediated metabolic reprogramming[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101559

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Flavonoid Compounds from Shenrong Guben Huanshao Pill alleviates senescence-associated mitochondrial dysfunction through NDUFV2 and LDHB mediated metabolic reprogramming

doi: 10.1016/j.jpha.2026.101559

a. School of basic medical sciences, Lanzhou University, Lanzhou, 73000, China;
b. Department of Medical Oncology, Gansu Cancer Hospital, Lanzhou, 73000, China;
c. Department of Radiation Oncology, Huashan Hospital, Fudan University, Shanghai, 201107, China;
d. National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, 200040, China;
e. Lanzhou Foci Pharmaceutical Co., LTD., 2289 Huashan Road, Lanzhou New District, Lanzhou, China;
f. School of Pharmacy, Lanzhou University, Lanzhou, 73000, China

Funds:

The authors would like to thank Medical Experiment Center of Lanzhou University and New Medical Science Innovation Platform of Lanzhou University for use of experimental equipment. This work was financially supported by National Natural Science Foundation of China (Grant Nos.: 82471640, and 82573229), National Key Research and Development Program of China (Grant No.: 2021YFF0702400) and Gansu Provincial Natural Science Foundation Specialized Project on Laboratory Animals (Grant No.: 25JRRA725).

Received Date: Sep. 25, 2025
Accepted Date: Jan. 20, 2026
Rev Recd Date: Jan. 19, 2026
Available Online: Jan. 22, 2026

Abstract

Abstract

Senescence is widely recognized as a key driving factor in the onset and progression of many chronic diseases. Although numerous animal studies have demonstrated that various drugs can delay senescence, their clinical application is severely limited due to significant toxic side effects. As a result, developing safer, natural anti-senescence agents has become an urgent priority. In this study, we identified mitochondrial dysfunction as a critical contributor to cellular senescence. In addition, we identified Shenrong Guben Huanshao Pill (SRW) as an effective agent that alleviates mitochondrial dysfunction and consequently delays cellular senescence by regulating mitochondrial metabolism. Mechanistically, SRW enhances mitochondrial function by upregulating the expression of NADH:ubiquinone oxidoreductase subunit V2 (NDUFV2), a core component of mitochondrial respiratory chain complex I. Simultaneously, SRW reduces lactate-induced mitochondrial dysfunction by regulating the glycolytic enzyme lactate dehydrogenase B (LDHB), thereby decreasing lactate accumulation. Collectively, our findings indicate that SRW alleviates cellular senescence by coordinately regulating NDUFV2 expression and LDHB-mediated lactate metabolism to improve mitochondrial function. In addition, several flavonoids in SRW were identified to possess potential anti-senescence activity. Molecular docking and cellular experiments confirmed that myricetin, luteolin, and gamma-mangostin effectively alleviate cellular senescence.
- Shenrong Guben Huanshao Pill (SRW),
- Senescence,
- Mitochondrial,
- NDUFV2,
- LDHB,
- Lactate

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References(42)

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