Although medicine and pharmacology have tremendously progressed over the past few decades, there are still no effective treatment options for certain complex diseases, including cancer, diabetes, and hepatic fibrosis. Researchers, however, continue to reveal mechanisms contributing to the development of these diseases, as well as potential drug targets, helping us develop better therapies. The latest issue of the Journal of Pharmaceutical Analysis features three articles on cutting-edge research targeting challenging diseases.
The first study, made available online in June 2022 and published in Volume 12, Issue 4 of the journal in 1st August 2022, was conducted by researchers from China and Singapore. They focused on 18beta-glycyrrhetinic acid (18β-GA), a compound naturally occurring in the plant Glycyrrhiza uralensis Fisch, whose root is widely used in traditional Asian medicine to treat hepatic diseases. Through multiple experiments, they demonstrated that 18β-GA can induce cell death in hepatic stellate cells, which are drivers of hepatic fibrosis, by targeting the antioxidants peroxiredoxin 1 and 2 and triggering oxidative stress in the cells. This has important medical implications, as the researchers commented: "Our findings provide strong evidence for the further development of 18β-GA as a therapeutic drug for the treatment of hepatic fibrosis. Understanding the underlying mechanisms of disease development have helped develop better therapeutics for liver diseases, which lead to almost 2 million deaths worldwide every year."
In the second article, a review which was made available online in April 2022 and published in Volume 12, Issue 4 of the journal in 1st August 2022, researchers from India summarized the latest knowledge on the role of human islet amyloid polypeptide (hIAPP) in the progression of type-2 diabetes mellitus (T2DM). The misfolding and aggregation of hIAPP into amyloid fibrils in the pancreas is one of the pathological hallmarks of T2DM and understanding why it happens, how it affects pancreatic cells, and how it can be stopped or reverted is essential in the context of T2DM. "Designing drugs that prevent hIAPP aggregation or that can eliminate already formed amyloid aggregates would likely help in the management of T2DM. Moreover, these drugs could be repurposed in the future for targeting other protein-misfolding disorders because of the common mechanism underlying these pathologies," the researchers remarked.
In the final study, made available online in January 2022 and published in Volume 12, Issue 4 of the journal in 1st August 2022, researchers from China screened 43 fluoroquinolone derivatives and tested them as microRNA-21 inhibitors to find a promising anti-cancer compound. Many types of tumor cells overexpress microRNA-21, making it a potential drug target in cancer therapy. Out of all the compounds tested, one named 'A36' proved to be the best microRNA-21 inhibitor. Cell culture experiments showed that A36 produced many of the outcomes that one would hope for in a cancer drug. "At the cellular level, A36 displayed moderate antiproliferative activity against six tumor cell lines, significantly induced apoptosis, arrested cell division, and inhibited colony formation of cancer cells, but exhibited no cytotoxic effects in healthy cell lines," the researchers highlighted.
In summary, these studies help explain the pathogenesis of complex diseases like diabetes, cancer, and liver fibrosis while exploring new approaches of treatment and drug targets. Further research in this field will eventually help doctors treat people who suffer from these complex diseases.
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Reference
DOI: https://doi.org/10.1016/j.jpha.2022.06.001
Authors: Qian Zhang1,3, Piao Luo1,3, Liuhai Zheng3, Jiayun Chen1, Junzhe Zhang1, Huan Tang1, Dandan Liu1, Xueling He1, Qiaoli Shi1, Liwei Gu1, Jiahao Li1, Qiuyan Guo1, Chuanbin Yang3, Yin Kwan Wong2, Fei Xia1, Jigang Wang1
Affiliations:
1Artemisinin Research Center and Institute of Chinese Materia Medica, Chinese Academy of Chinese Medical Sciences
2Department of Biological Sciences, National University of Singapore
3Department of Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University)
