Cryptococcosis is an infectious disease of global significance for which new therapies are needed. Repurposing previously developed drugs for new indications can expedite the translation of new therapies from bench to beside. Here, we characterized the anti-cryptococcal activity and antifungal mechanism of estrogen receptor antagonists related to the breast cancer drugs tamoxifen and toremifene. Tamoxifen and toremifene are fungicidal and synergize with fluconazole and amphotericin B in vitro. In a mouse model of disseminated cryptococcosis, tamoxifen at concentrations achievable in humans combines with fluconazole to decrease brain burden by ~1 log10. In addition, these drugs inhibit the growth of Cryptococcus neoformans within macrophages, a niche not accessible by current antifungal drugs. Toremifene and tamoxifen directly bind to the essential EF hand protein calmodulin, as determined by thermal shift assays with purified C. neoformans calmodulin (Cam1), prevent Cam1 from binding to its well-characterized substrate calcineurin (Cna1), and block Cna1 activation. In whole cells, toremifene and tamoxifen block the calcineurin-dependent nuclear localization of the transcription factor Crz1. A large-scale chemical genetic screen with a library of C. neoformans deletion mutants identified a second EF hand-containing protein, which we have named calmodulin-like protein 1 (CNAG_05655), as a potential target, and further analysis showed that toremifene directly binds Cml1 and modulates its ability to bind and activate Cna1. Importantly, tamoxifen analogs (idoxifene and methylene-idoxifene) with increased calmodulin antagonism display improved anti-cryptococcal activity, indicating that calmodulin inhibition can be used to guide a systematic optimization of the anti-cryptococcal activity of the triphenylethylene scaffold.

There are more than 30 species of Glycyrrhiza genus extensively spread worldwide. It was the most prescribed herb in Ancient Egyptian, Roman, Greek, East China, and the West from the Former Han era. There are various beneficial effects of licorice root extracts, such as treating throat infections, tuberculosis, respiratory, liver diseases, antibacterial, anti-inflammatory, and immunodeficiency. On the other hand, traditional medicines are getting the attraction to treat many diseases. Therefore, it is vital to screen the medicinal plants to find the potential of new compounds to treat chronic diseases such as respiratory, cardiovascular, anticancer, hepatoprotective, etc. This work comprehensively reviews ethnopharmacological uses, phytochemistry, biological activities, clinical evidence, and the toxicology of licorice, which will serve as a resource for future clinical and fundamental studies. An attempt has been made to establish the pharmacological effect of licorice in different diseases. In addition, the focus of this review article is on the molecular mechanism of licorice extracts and their four flavonoids (isoliquiritigenin, liquiritigenin, lichalocone, and glabridin) pharmacologic activities. Licorice could be a natural alternative for current therapy to exterminate new emerging disorders with mild side effects. This review will provide systematic insights into this ancient drug for further development and clinical use.

Background A dramatic increase in the use of natural products and herbal medicines has been observed globally. Simultaneously, there has been an increase in safety concerns regarding the extensive use of these herbal remedies among health care practitioners. The urban and rural populations of Saudi Arabia still rely on traditional Arabic herbal medicines for the treatment of various diseases. Objectives This study aimed to evaluate community pharmacists' knowledge, attitudes, and practices of herbal medicines in the Asir region, Saudi Arabia. Methods An online cross-sectional study was conducted among 233 community pharmacists using a structured questionnaire. Results Pharmacists showed considerable knowledge of the indications of herbal products, with an average score of 84% correct answers, total P value < 0.05 and < 0.001. They were also knowledgeable about contraindications, side effects, and interactions, with an average score of 75% correct answers, total P value < 0.05 and < 0.001. Community pharmacists had a positive attitude towards herbal products, as 71% of them “agreed” or “strongly agreed” that herbal products were efficacious and 77% of them “agreed” or “strongly agreed” that those products should be sold only in a pharmacy. Herbal products were “often” or "always” dispensed by 67.3% of pharmacists in a pharmacy. Conclusion Pharmacists generally exhibited good knowledge, a positive attitude, and effective practice towards herbal products. However, continuing education programs are needed to train pharmacists in providing client counseling on herbal medicine usage and dispensing them.

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Respiratory tract infections are underestimated, as they are mild and generally not incapacitating. In clinical medicine, however, these infections are considered a prevalent problem. By 2030, the third most comprehensive reason for death worldwide will be chronic obstructive pulmonary disease (COPD), according to the World Health Organization. The current arsenal of anti-inflammatory drugs shows little or no benefits against COPD. For thousands of years, herbal drugs have been used to cure numerous illnesses; they exhibit promising results and enhance physical performance. Ginseng is one such herbal medicine, known to alleviate pro-inflammatory chemokines and cytokines (IL-2, IL-4, IFN-γ, TNF-α, IL-5, IL-6, IL-8) formed by macrophages and epithelial cells. Furthermore, the mechanisms of action of ginsenoside are still not fully understood. Various clinical trials of ginseng have exhibited a reduction of repeated colds and the flu. In this review, ginseng’s structural features, the pathogenicity of microbial infections, and the immunomodulatory, antiviral, and anti-bacterial effects of ginseng were discussed. The focus was on the latest animal studies and human clinical trials that corroborate ginseng’s role as a therapy for treating respiratory tract infections. The article concluded with future directions and significant challenges. This review would be a valuable addition to the knowledge base for researchers in understanding the promising role of ginseng in treating respiratory tract infections. Further analysis needs to be re-focused on clinical trials to study ginseng’s efficacy and safety in treating pathogenic infections and in determining ginseng-drug interactions.