Journal of Pharmaceutical Analysis (JPA) Studies Find Promising Drug Candidates

Researchers investigate the intricacies of various cellular processes and pathologies and identify compounds with untapped therapeutic potential

XI'AN, China, March 29, 2024 /PRNewswire/ -- Understanding the underlying mechanisms of normal and pathological cellular processes is essential for developing new drugs. Fortunately, modern techniques and experimental methods have greatly accelerated progress. The latest issue of JPA features three articles in which candidate compounds for treating complex disorders were successfully identified, alongside their detailed mechanisms of action.

The first study investigated the use of metformin (Met), a drug used to manage type II diabetes, for treating benign prostate hyperplasia (BPH). The article was published in Volume 14, Issue 1 of the journal in January 2024. The researchers first sought to shed light on how and which dysregulated sex steroid hormone-related pathways shape the pathological characteristics of BPH, and whether Met can restore these pathways.

Through retrospective analysis of data from BPH patients and clinical assessment of serum and tissue samples, the researchers identified dihydrotestosterone (DHT) as a major contributor to BPH among dysregulated sex hormones. DHT promotes prostate cell proliferation by upregulating androgen receptors and forming YAP1-TEAD4 heterodimers. In vivo experiments showed that Met treatment restored sex hormone homeostasis and inhibited DHT-induced cell proliferation. "Our study provided strong evidence that Met might be a promising clinical therapeutic approach for the treatment of BPH," remark corresponding authors Prof. Qian Lu and Prof. Xiaoxing Yin.

In the second study, scientists explored the role of epimedin B (EB), the main flavonoid in the Chinese herb Epimedium brevicornum Maxim., in melanogenesis. They expanded on previous findings showing EB's ability to induce melanogenesis and activate tyrosinase family of proteins (TYRs). Through comprehensive in vitro and in vivo experiments on human and animal cells, they uncovered how EB modulated TYRs, increased melanosome numbers, promoted maturation, and aided depigmentation and repigmentation. "Our data reveals that EB can stimulate the pigmentation function of TYRs, which might provide a novel rational strategy for hypopigmentation treatment in the pharmaceutical and cosmetic industries," comments corresponding authors Dr. Yiming Li and Prof. Huali Wu.

Finally, in the third study, researchers investigated ferroptosis, a type of programmed cell death, and its role in nerve regeneration after peripheral nerve injury (PNI). They found that oxidative stress at the injury site not only triggered both apoptosis and ferroptosis in nearby neurons by increasing intracellular iron via the degradation of ferroportin by UBA52. Using the Drug Signatures Database, they identified hydralazine (HYD), a potent arterial vasodilator, as a potential UBA52 disruptor. Early HYD administration after PNI in vivo expedited axon regeneration and motor function recovery, partly by suppressing ferroptosis. "The potential clinical implementation of HYD may lead to a reduction in the prevalence of individuals with mild symptoms of nerve damage, consequently mitigating the societal burden," conclude corresponding authors Dr. Bing Xia, Prof. Zhuojing Luo, and Dr. Jinghui Huang.

Further studies will hopefully clarify the intricate connections among cellular processes, diseases, and potential drugs, paving the way for precise and efficient therapies.

Reference

Titles of original papers

1. Metformin: A promising clinSical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation
2. Epimedin B exhibits pigmentation by increasing tyrosinase family proteins expression, activity, and stability
3. Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52

Journal: Journal of Pharmaceutical Analysis

DOI

1. https://doi.org/10.1016/j.jpha.2023.08.012
2. https://doi.org/10.1016/j.jpha.2023.09.006
3. https://doi.org/10.1016/j.jpha.2023.08.006

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SOURCE Journal of Pharmaceutical Analysis (JPA)