In the last decade, messenger ribonucleic acid (mRNA)-based drugs have gained great interest in both immunotherapy and non-immunogenic applications. This surge in interest can be largely attributed to the demonstration of distinct advantages offered by various mRNA molecules, alongside the rapid advancements in nucleic acid delivery systems. It is noteworthy that the immunogenicity of mRNA drugs presents a double-edged sword. In the context of immunotherapy, extra supplementation of adjuvant is generally required for induction of robust immune responses. Conversely, in non-immunotherapeutic scenarios, immune activation is unwanted considering the host tolerability and high expression demand for mRNA-encoded functional proteins. Herein, mainly focused on the linear non-replicating mRNA, we overview the preclinical and clinical progress and prospects of mRNA medicines encompassing vaccines and other therapeutics. We also highlight the importance of focusing on the host-specific variations, including age, gender, pathological condition, and concurrent medication of individual patient, for maximized efficacy and safety upon mRNA administration. Furthermore, we deliberate on the potential challenges that mRNA drugs may encounter in the realm of disease treatment, the current endeavors of improvement, as well as the application prospects for future advancements. Overall, this review aims to present a comprehensive understanding of mRNA-based therapies while illuminating the prospective development and clinical application of mRNA drugs.
Many common diseases like diabetes, cardiovascular disease, and cancer are caused or exacerbated by disparate physiological, pathological, environmental, and lifestyle factors. However, the chief aim of current drug discovery approaches is to search for single-entity drugs that interact with well-defined molecular targets (a single receptor or enzyme). The concept of multi-target drugs or multi-component therapy is gaining increased attention with the discovery that many diseases (like hypertension) are best treated by multi-drug or multi-target therapies. Traditional medicines, such as traditional Chinese medicine (TCM) and Indian Ayurveda, have been re-evaluated and are becoming important resources for the discovery of bioactive molecules with therapeutic effects and for designing multi-targets drugs. This article provides an overview of new strategies and techniques to design therapeutic regimes that comprise more than one active ingredient to produce synergistic effects by simultaneously interacting with multiple molecular targets. Advances in phytochemistry, high throughput screening, DNA sequencing, systems biology, and bioinformatics can reveal the chemical composition and molecular mechanisms of TCM and together provide a new template for the early stages of drug discovery. Meanwhile, clinical knowledge of TCM provides a promising framework for multi-component drug design. A renaissance of multi-component drug discovery inspired by traditional medicine is possible.
1 January 2011 in Evidence-Based Complementary and Alternative Medicine
Psoralea corylifolia L. (Fabaceae) is a widely used medical plant in China. This study was designed to screen and identify bioactive compounds with anticancer activity from the seeds of Psoralea corylifolia L. One volatile fraction (fraction I) and three other fractions (fraction II, III, IV) from methanol extraction of P. corylifolia L. were obtained. Bioactivities of these fractions were evaluated by the cytotoxicity on KB, KBv200, K562, K562/ADM cancer cells with MTT assay. Major components in the active fraction were identified by HPLC/MSn. Fraction IV significantly inhibits the growth of cancer cells in a dose‐dependent manner. The IC50 values were 21.6, 24.4, 10.0 and 26.9, respectively. Psoralen and isopsoralen, isolated from fraction IV, were subject to bioactive assay and presented a dose‐dependent anticancer activity in four cancer cell lines (KB, KBv200, K562 and K562/ADM). The IC50 values of psoralen were 88.1, 86.6, 24.4 and 62.6, which of isopsoralen were 61.9, 49.4, 49.6 and 72.0, respectively. Apoptosis of tumor cell significantly increased after treated with psoralen and isopsoralen. Induction of apoptotic activity was confirmed by flow cytometry after staining with Annexin V/PI. These results suggested psoralen and isopsoralen contribute to anticancer effect of P. corylifolia L.