Traditional uses, phytochemistry, pharmacology and toxicology of garlic (Allium sativum), a storehouse of diverse phytochemicals: A review of research from the last decade focusing on health and nutritional implications

Allium sativum L. (Garlic) is a fragrant herb and tuber-derived spice that is one of the most sought-after botanicals, used as a culinary and ethnomedicine for a variety of diseases around the world. An array of pharmacological attributes such as antioxidant, hypoglycemic, anti-inflammatory, antihyperlipidemic, anticancer, antimicrobial, and hepatoprotective activities of this species have been established by previous studies. A. sativum houses many sulfur-containing phytochemical compounds such as allicin, diallyl disulfide (DADS), vinyldithiins, ajoenes (E-ajoene, Z-ajoene), diallyl trisulfide (DATS), micronutrient selenium (Se) etc. Organosulfur compounds are correlated with modulations in its antioxidant properties. The garlic compounds have also been recorded as promising immune-boosters or act as potent immunostimulants. A. sativum helps to treat cardiovascular ailments, neoplastic growth, rheumatism, diabetes, intestinal worms, flatulence, colic, dysentery, liver diseases, facial paralysis, tuberculosis, bronchitis, high blood pressure, and several other diseases. The present review aims to comprehensively enumerate the ethnobotanical and pharmacological aspects of A. sativum with notes on its phytochemistry, ethnopharmacology, toxicological aspects, and clinical studies from the retrieved literature from the last decade with notes on recent breakthroughs and bottlenecks. Future directions related to garlic research is also discussed.This work was supported by the UHK (Project No. VT2019- 2021), APOGEO (Cooperation Program INTERREG-MAC 2014–2020), with European Funds for Regional Development- FEDER, the “Agencia Canaria de Investigación, Innovación y Sociedad de la Información (ACIISI) Gobierno de Canarias” (Project No. ProID2020010134), and Caja Canarias (Project No. 2019SP43).Peer reviewe

Rapamycin: Drug Repurposing in SARS-CoV-2 Infection

Since December 2019, SARS-CoV-2 (COVID-19) has been a worldwide pandemic with enormous consequences for human health and the world economy. Remdesivir is the only drug in the world that has been approved for the treating of COVID-19. This drug, as well as vaccination, still has uncertain effectiveness. Drug repurposing could be a promising strategy how to find an appropriate molecule: rapamycin could be one of them. The authors performed a systematic literature review of available studies on the research describing rapamycin in association with COVID-19 infection. Only peer-reviewed English-written articles from the world’s acknowledged databases Web of Science, PubMed, Springer and Scopus were involved. Five articles were eventually included in the final analysis. The findings indicate that rapamycin seems to be a suitable candidate for drug repurposing. In addition, it may represent a better candidate for COVID-19 therapy than commonly tested antivirals. It is also likely that its efficiency will not be reduced by the high rate of viral RNA mutation

Novel CRISPR–Cas Systems: An Updated Review of the Current Achievements, Applications, and Future Research Perspectives

According to Darwin’s theory, endless evolution leads to a revolution. One such example is the Clustered Regularly Interspaced Palindromic Repeats (CRISPR)–Cas system, an adaptive immunity system in most archaea and many bacteria. Gene editing technology possesses a crucial potential to dramatically impact miscellaneous areas of life, and CRISPR–Cas represents the most suitable strategy. The system has ignited a revolution in the field of genetic engineering. The ease, precision, affordability of this system is akin to a Midas touch for researchers editing genomes. Undoubtedly, the applications of this system are endless. The CRISPR–Cas system is extensively employed in the treatment of infectious and genetic diseases, in metabolic disorders, in curing cancer, in developing sustainable methods for fuel production and chemicals, in improving the quality and quantity of food crops, and thus in catering to global food demands. Future applications of CRISPR–Cas will provide benefits for everyone and will save countless lives. The technology is evolving rapidly; therefore, an overview of continuous improvement is important. In this review, we aim to elucidate the current state of the CRISPR–Cas revolution in a tailor-made format from its discovery to exciting breakthroughs at the application level and further upcoming trends related to opportunities and challenges including ethical concerns

Neuropharmacology of Cevimeline and Muscarinic Drugs—Focus on Cognition and Neurodegeneration

At present, Alzheimer’s disease (AD) and related dementias cannot be cured. Therefore, scientists all over the world are trying to find a new approach to prolong an active life of patients with initial dementia. Both pharmacological and non-pharmacological pathways are investigated to improve the key symptom of the disease, memory loss. In this respect, influencing the neuromodulator acetylcholine via muscarinic receptors, such as cevimeline, might be one of the therapeutic alternatives. The purpose of this study is to explore the potential of cevimeline on the cognitive functions of AD patients. The methodology is based on a systematic literature review of available studies found in Web of Science, PubMed, Springer, and Scopus on the research topic. The findings indicate that cevimeline has shown an improvement in experimentally induced cognitive deficits in animal models. Furthermore, it has demonstrated to positively influence tau pathology and reduce the levels of amyloid-β (Aβ) peptide in the cerebral spinal fluid of Alzheimer’s patients. Although this drug has not been approved by the FDA for its use among AD patients and there is a lack of clinical studies confirming and extending this finding, cevimeline might represent a breakthrough in the treatment of AD

Mechanistic Insight into Antimicrobial and Antioxidant Potential of Jasminum Species: A Herbal Approach for Disease Management

Drug resistance among microbial pathogens and oxidative stress caused by reactive oxygen species are two of the most challenging global issues. Firstly, drug-resistant pathogens cause several fatalities every year. Secondly aging and a variety of diseases, such as cardiovascular disease and cancer, are associated with free radical generated oxidative stress. The treatments currently available are limited, ineffective, or less efficient, so there is an immediate need to tackle these issues by looking for new therapies to resolve resistance and neutralize the harmful effects of free radicals. In the 21st century, the best way to save humans from them could be by using plants as well as their bioactive constituents. In this specific context, Jasminum is a major plant genus that is used in the Ayurvedic system of medicine to treat a variety of ailments. The information in this review was gathered from a variety of sources, including books, websites, and databases such as Science Direct, PubMed, and Google Scholar. In this review, a total of 14 species of Jasminum have been found to be efficient and effective against a wide variety of microbial pathogens. In addition, 14 species were found to be active free radical scavengers. The review is also focused on the disorders related to oxidative stress, and it was concluded that Jasminum grandiflorum and J. sambac normalized various parameters that were elevated by free radical generation. Alkaloids, flavonoids (rutoside), terpenes, phenols, and iridoid glucosides are among the main phytoconstituents found in various Jasminum species. Furthermore, this review also provides insight into the mechanistic basis of drug resistance, the generation of free radicals, and the role of Jasminum plants in combating resistance and neutralizing free radicals

Antifungal Nano-Therapy in Veterinary Medicine: Current Status and Future Prospects

The global recognition for the potential of nanoproducts and processes in human biomedicine has given impetus for the development of novel strategies for rapid, reliable, and proficient diagnosis, prevention, and control of animal diseases. Nanomaterials exhibit significant antifungal and antimycotoxin activities against mycosis and mycotoxicosis disorders in animals, as evidenced through reports published over the recent decade and more. These nanoantifungals can be potentially utilized for the development of a variety of products of pharmaceutical and biomedical significance including the nano-scale vaccines, adjuvants, anticancer and gene therapy systems, farm disinfectants, animal husbandry, and nutritional products. This review will provide details on the therapeutic and preventative aspects of nanoantifungals against diverse fungal and mycotoxin-related diseases in animals. The predominant mechanisms of action of these nanoantifungals and their potential as antifungal and cytotoxicity-causing agents will also be illustrated. Also, the other theragnostic applications of nanoantifungals in veterinary medicine will be identified

Applications of Fruit Polyphenols and Their Functionalized Nanoparticles Against Foodborne Bacteria: A Mini Review

The ingestion of contaminated water and food is known to cause food illness. Moreover, on assessing the patients suffering from foodborne disease has revealed the role of microbes in such diseases. Concerning which different methods have been developed for protecting food from microbes, the treatment of food with chemicals has been reported to exhibit an unwanted organoleptic effect while also affecting the nutritional value of food. Owing to these challenges, the demand for natural food preservatives has substantially increased. Therefore, the interest of researchers and food industries has shifted towards fruit polyphenols as potent inhibitors of foodborne bacteria. Recently, numerous fruit polyphenols have been acclaimed for their ability to avert toxin production and biofilm formation. Furthermore, various studies have recommended using fruit polyphenols solely or in combination with chemical disinfectants and food preservatives. Currently, different nanoparticles have been synthesized using fruit polyphenols to curb the growth of pathogenic microbes. Hence, this review intends to summarize the current knowledge about fruit polyphenols as antibacterial agents against foodborne pathogens. Additionally, the application of different fruit extracts in synthesizing functionalized nanoparticles has also been discussed

Discovery of small molecule mechanistic target of rapamycin inhibitors as anti-aging and anti-cancer therapeutics

To date, the most studied drug in anti-aging research is the mTOR inhibitor – rapamycin. Despite its almost perfect anti-aging profile, rapamycin exerts one significant limitation – inappropriate physicochemical properties. Therefore, we have decided to utilize virtual high-throughput screening and fragment-based design in search of novel mTOR inhibiting scaffolds with suitable physicochemical parameters. Seven lead compounds were selected from the list of obtained hits that were commercially available (4, 5, and 7) or their synthesis was feasible (1, 2, 3, and 6) and evaluated in vitro and subsequently in vivo. Of all these substances, only compound 3 demonstrated a significant cytotoxic, senolytic, and senomorphic effect on normal and cancerous cells. Further, it has been confirmed that compound 3 is a direct mTORC1 inhibitor. Last but not least, compound 3 was found to exhibit anti-SASP activity concurrently being relatively safe within the test of in vivo tolerability. All these outstanding results highlight compound 3 as a scaffold worthy of further investigation

Privileged multi-target directed propargyl-tacrines combining cholinesterase and monoamine oxidase inhibition activities

Twenty-four novel compounds bearing tetrahydroacridine and N-propargyl moieties have been designed, synthesised, and evaluated in vitro for their anti-cholinesterase and anti-monoamine oxidase activities. Propargyltacrine 23 (IC50 = 21 nM) was the most potent acetylcholinesterase (AChE) inhibitor, compound 20 (IC50 = 78 nM) showed the best inhibitory human butyrylcholinesterase (hBChE) profile, and ligand 21 afforded equipotent and significant values on both ChEs (human AChE [hAChE]: IC50 = 0.095 ± 0.001 µM; hBChE: IC50 = 0.093 ± 0.003 µM). Regarding MAO inhibition, compounds 7, 15, and 25 demonstrated the highest inhibitory potential towards hMAO-B (IC50 = 163, 40, and 170 nM, respectively). In all, compounds 7, 15, 20, 21, 23, and 25 exhibiting the most balanced pharmacological profile, were submitted to permeability and cell viability tests. As a result, 7-phenoxy-N-(prop-2-yn-1-yl)-1,2,3,4-tetrahydroacridin-9-amine hydrochloride (15) has been identified as a permeable agent that shows a balanced pharmacological profile [IC50 (hAChE) = 1.472 ± 0.024 µM; IC50 (hBChE) = 0.659 ± 0.077 µM; IC50 (hMAO-B) = 40.39 ± 5.98 nM], and consequently, as a new hit-ligand that deserves further investigation, in particular in vivo analyses, as the preliminary cell viability test results reported here suggest that this is a relatively safe therapeutic agent. </p

Frentizole derivatives with mTOR inhibiting and senomorphic properties

Frentizole is immunosuppressive drug with low acute toxicity and lifespan-prolonging effect. Recently, frentizole´s potential to disrupt toxic amyloid β (Aβ) - Aβ-binding alcohol dehydrogenase (ABAD) interaction in mitochondria in Alzheimer´s brains has been revealed. Another broadly studied drug with anti-aging and immunosuppressive properties is an mTOR inhibitor – rapamycin. Since we do not yet precisely know what is behind the lifespan-prolonging effect of rapamycin and frentizole, whether it is the ability to inhibit the mTOR signaling pathway, reduction in mitochondrial toxicity, immunosuppressive effect, or a combination of all of them, we have decided within our previous work to dock the entire in-house library of almost 240 Aβ-ABAD modulators into the FKBP-rapamycin-binding (FRB) domain of mTOR in order to interlink mTOR-centric and mitochondrial free radical-centric theories of aging and thus to increase the chances of success. Based on the results of the docking study, molecular dynamic simulation and MM-PBSA calculations, we have selected nine frentizole-like compounds (1 – 9). Subsequently, we have determined their real physical-chemical properties (logP, logD, pKa and solubility in water and buffer), cytotoxic/cytostatic, mTOR inhibitory, and in vitro anti-senescence (senolytic and senomorphic) effects. Finally, the three best candidates (4, 8, and 9) have been forwarded for in vivo safety studies to assess their acute toxicity and pharmacokinetic properties. Based on obtained results, only compound 4 demonstrated the best results within in vitro testing, the ability to cross the blood-brain barrier and the lowest acute toxicity (LD50 in male mice 559 mg/kg; LD50 in female mice 575 mg/kg)