Advances on Natural Abietane, Labdane and Clerodane Diterpenes as Anti-Cancer Agents: Sources and Mechanisms of Action

Molecules 2022, 27(15), 4791

Extensive research over the past decades has identified numerous phytochemicals that could represent an important source of anti-cancer compounds. There is an immediate need for less toxic and more effective preventive and therapeutic strategies for the treatment of cancer. Natural compounds are considered suitable candidates for the development of new anti-cancer drugs due to their pleiotropic actions on target events with multiple manners. This comprehensive review highlighted the most relevant findings achieved in the screening of phytochemicals for anticancer drug development, particularly focused on a promising class of phytochemicals such as diterpenes with abietane, clerodane, and labdane skeleton. The chemical structure of these compounds, their main natural sources, and mechanisms of action were critically discussed.

Essential oils nano-emulsion confers resistance against Penicillium digitatum in 'Newhall' navel orange by promoting phenylpropanoid metabolism

 Industrial Crops and Products, 187(A), 115297, 2022

Inducing natural resistance against pathogen infection in postharvest citrus by exogenous elicitor is a promising alternative to reduce postharvest losses. Here, the potential induced resistance mechanism of blended cinnamaldehyde, carvacrol and eugenol nano-emulsion against P. digitatum in ‘Newhall’ navel orange (Citrus sinensis (L.) Osbeck) was evaluated through combined transcriptomic and metabolomics analysis. Application of nano-emulsion maintained fruit firmness after P. digitatum inoculation, nano-emulsion reduced H2O2 and MDA accumulation of citrus fruit, increased PAL, C4H, 4CL and CAD activity, and higher contents of flavonoids, lignin and total phenolic compounds. Furthermore, higher activities of SOD, CAT, POD and APX in nano-emulsion treated fruit possibly benefited reducing ROS accumulation and lipid peroxidation. The activities of the defense enzymes CHI, GLU were higher in the nano-emulsion treated fruits. RNA-seq identified 653 differentially expressed genes (DEGs) between the control and the nano-emulsion-treated fruit at 48 hpi, including 444 up-regulated and 209 downregulated genes. Genes encoding shikimate O-hydroxycinnamoyltransferase (HCT), caffeoyl-CoA O-methyltransferase (CCoAOMT), caffeic acid 3-O-methyltransferase / acetylserotonin O-methyltransferase (COMT), cinnamyl-alcohol dehydrogenase (CAD) and peroxidase (POD) were differentially expressed by nano-emulsion treatment. In addition, 175 differential accumulated metabolites between the control and the nano-emulsion-treated fruit at 48 hpi also were identified, the different accumulated metabolites from phenylpropanoid biosynthesis pathway related with disease resistance including L-phenylalanine, caffeic acid, caffeoyl quinic acid, coniferyl alcohol, coniferaldehyde. The integrated transcriptomic and metabolomic profiling indicated that the differentially expressed genes (DEGs) and the differentially accumulated metabolites (DAMs) were mainly involved in phenylpropanoid biosynthesis pathway. Besides, the nano-emulsion significantly induced accumulation of primary metabolites including amino acids, soluble sugars, organic acids, lipids, sugar and alcohols. All these results indicated that blended essential oil nano-emulsion as an antifungal delivery system to induce resistance against P. digitatum infection of ‘Newhall’ navel orange by promoting phenylpropanoid metabolism.

The influence of phytochemicals on cell heterogeneity in chronic inflammation-associated diseases: the prospects of single cell sequencing

 The Journal of Nutritional Biochemistry, 108, 109091, 2022

Chronic inflammation-associated diseases include, but is not limited to cardiovascular disease, cancer, obesity, diabetes, etc. Cell heterogeneity is a prerequisite for understanding the physiological and pathological development of cell metabolism, and its response to external stimuli. Recently, dietary habits based on phytochemicals became increasingly recognized to play a pivotal role in chronic inflammation. Phytochemicals can relieve chronic inflammation by regulating inflammatory cell differentiation and immune cell response, but the influence of phytochemicals on cell heterogeneity from in vitro and ex vivo studies cannot simulate the complexity of cell differentiation in vivo due to the differences in cell lines and extracellular environment. Therefore, there is no consensus on the regulation mechanism of phytochemicals on chronic diseases based on cell heterogeneity. The purpose of this review is to summarize cell heterogeneity in common chronic inflammation-associated diseases and trace the effects of phytochemicals on cell differentiation in chronic diseases development. More importantly, by discussing the problems and challenges which hinder the study of cell heterogeneity in recent nutritional assessment experiments, we propose new prospects based on the drawbacks of existing research to optimize the research on the regulation mechanism of phytochemicals on chronic diseases. The need to explore precise measurements of cell heterogeneity is a key pillar in understanding the influence of phytochemicals on certain diseases. In the future, deeper understanding of cell-to-cell variation and the impact of food components and their metabolites on cell function by single-cell genomics and epigenomics with the focus on individual differences will open new avenues for the next generation of health care.

Biological properties and potential of compounds extracted from red seaweeds

 Phytochemistry Reviews, 2022

Macroalgae have been recently used for different applications in the food, cosmetic and pharmaceutical industry since they do not compete for land and freshwater against other resources. Moreover, they have been highlighted as a potential source of bioactive compounds. Red algae (Rhodophyta) are the largest group of seaweeds, including around 6000 different species, thus it can be hypothesized that they are a potential source of bioactive compounds. Sulfated polysaccharides, mainly agar and carrageenans, are the most relevant and exploited compounds of red algae. Other potential molecules are essential fatty acids, phycobiliproteins, vitamins, minerals, and other secondary metabolites. All these compounds have been demonstrated to exert several biological activities, among which antioxidant, anti-inflammatory, antitumor, and antimicrobial properties can be highlighted. Nevertheless, these properties need to be further tested on in vivo experiments and go in-depth in the study of the mechanism of action of the specific molecules and the understanding of the structure–activity relation. At last, the extraction technologies are essential for the correct isolation of the molecules, in a cost-effective way, to facilitate the scale-up of the processes and their further application by the industry. This manuscript is aimed at describing the fundamental composition of red algae and their most studied biological properties to pave the way to the utilization of this underused resource.