Current Topics in Medicinal Chemistry - Volume 24, Issue 12, 2024

Frequently occurring inflammatory skin conditions such as psoriasis, dermatitis, acne, including skin cancer, wounds and other disorders arising out of premature skin aging, deteriorate skin health and adversely impact human life. Even though several synthetic compounds have evolved for treating these skin conditions, natural-product-based therapeutics are gaining popularity with growing evidence of their efficacy and safety for treating skin disorders. Many of these inflammatory skin diseases have underlying disturbances in our immune system and immunomodulatory natural products provide solutions for their effective treatment and aid in understanding the underlying mechanism of such inflammatory skin conditions. Based on this premise, the present review summarizes the possible application of plant-derived immunomodulatory compositions and single molecules for treating inflammatory skin conditions. In vitro, in vivo and mechanistic studies reported the application of selected plant-derived natural products for the treatment of inflammatory skin disorders including, cancer and infections. Several online databases including PubMed, Google Scholar, and Science Direct have been searched for gathering the information covered in this review. Empirical studies demonstrated that most of these natural compounds exhibited therapeutic properties through their immunomodulatory and anti-inflammatory potential supplemented often with anti-microbial, anti-neoplastic, and anti- oxidant activities. Overall, plant-based natural products discussed here are capable of modulating the immune system to minimize or completely suppress the pro-inflammatory markers, scavenge free radicals (ROS), prevent bacteria, fungal, and virus-derived skin infections and often regress skin cancer through the induction of apoptosis. The challenges and opportunities associated with the application of plant-based immunomodulators for skin applications and their safety considerations are also discussed here. The present study indicated that immunomodulatory plant natural products being biologically validated ligands against various biological targets manifested in inflammatory skin diseases, offer an effective, safe and affordable treatment for such disorders affecting skin health. However, further clinical evaluations are needed to substantiate these findings.

During the last five decades, there has been tremendous development in our understanding of cancer biology and the development of new and novel therapeutics to target cancer. However, despite these advances, cancer remains the second leading cause of death across the globe. Most cancer deaths are attributed to the development of resistance to current therapies. There is an urgent and unmet need to address cancer therapy resistance. Tetrandrine, a bis-benzyl iso-quinoline, has shown a promising role as an anti-cancer agent. Recent work from our laboratory and others suggests that tetrandrine and its derivatives could be an excellent adjuvant to the current arsenal of anti-cancer drugs. Herein, we provide an overview of resistance mechanisms to current therapeutics and review the existing literature on the anti-cancer effects of tetrandrine and its potential use for overcoming therapy resistance in cancer.

Annually, a significant number of individuals succumb to cancer, an anomalous cellular condition characterized by uncontrolled cellular proliferation and the emergence of highly perilous tumors. Identifying underlying molecular mechanism(s) driving disease progression has led to various inventive therapeutic approaches, many of which are presently under pre-clinical and/or clinical trials. Over the recent years, numerous alternative strategies for addressing cancer have also been proposed and put into practice. This article delineates the modern therapeutic drugs employed in cancer treatment and their associated toxicity. Due to inherent drug toxicity associated with most modern treatments, demand rises for alternative therapies and phytochemicals with minimal side effects and proven efficacy against cancer. Analogs of taxol, Vinca alkaloids like vincristine and vinblastine, and podophyllotoxin represent a few illustrative examples in this context. The phytochemicals often work by modifying the activity of molecular pathways that are thought to be involved in the onset and progression of cancer. The principal objective of this study is to provide an overview of our current understanding regarding the pharmacologic effects and molecular targets of the active compounds found in natural products for cancer treatment and collate information about the recent advancements in this realm. The authors' interest in advancing the field of phytochemical research stems from both the potential of these compounds for use as drugs as well as their scientific validity. Accordingly, the significance of herbal formulations is underscored, shedding light on anticancer phytochemicals that are sought after at both pre-clinical and clinical levels, with discussion on the opportunities and challenges in pre-clinical and clinical cancer studies.

Background: Immunomodulation is the modification of immune responses to control disease progression. While the synthetic immunomodulators have proven efficacy, they are coupled with toxicity and other adverse effects, and hence, the efforts were to identify natural phytochemicals with immunomodulatory potential. Objective: To understand the immunomodulatory properties of various phytochemicals and investigate them in Echinacea species extracts using an in silico approach. Methodology: Several scientific database repositories were searched using different keywords: “Phytochemicals,” “Alkaloids,” “Polyphenols,” “Flavonoids,” “Lectins,” “Glycosides,” “Tannins,” “Terpenoids,” “Sterols,” “Immunomodulators,” and “Human Immune System” without any language restriction. Additionally, the study specifically investigated the immunomodulatory properties of Echinacea species extracts using gene expression analysis of GSE12259 from NCBI-GEO through the Bioconductor package GEOquery and limma. Results: A total of 182 studies were comprehensively analyzed to understand immunomodulatory phytochemicals. The in silico analysis highlighted key biological processes (positive regulation of cytokine production, response to tumor necrosis factor) and molecular functions (cytokine receptor binding, receptor-ligand activity, and cytokine activity) among Echinacea species extracts contributing to immune responses. Further, it also indicated the association of various metabolic pathways, i.e., pathways in cancer, cytokine-cytokine receptor interaction, NF-kappa B, PI3K-Akt, TNF, MAPK, and NOD-like receptor signaling pathways, with immune responses. The study revealed various hub targets, including CCL20, CCL4, GCH1, SLC7A11, SOD2, EPB41L3, TNFAIP6, GCLM, EGR1, and FOS. Conclusion: The present study presents a cumulative picture of phytochemicals with therapeutic benefits. Additionally, the study also reported a few novel genes and pathways in Echinacea extracts by re-analyzing GSE 12259 indicating its anti-inflammatory, anti-viral, and immunomodulatory properties.