Pharmacological Properties of Trichostatin A, Focusing on the Anticancer Potential: A Comprehensive Review.

Trichostatin A (TSA), a natural derivative of dienohydroxamic acid derived from a fungal metabolite, exhibits various biological activities. It exerts antidiabetic activity and reverses high glucose levels caused by the downregulation of brain-derived neurotrophic factor (BDNF) expression in Schwann cells, anti-inflammatory activity by suppressing the expression of various cytokines, and significant antioxidant activity by suppressing oxidative stress through multiple mechanisms. Most importantly, TSA exhibits potent inhibitory activity against different types of cancer through different pathways. The anticancer activity of TSA appeared in many in vitro and in vivo investigations that involved various cell lines and animal models. Indeed, TSA exhibits anticancer properties alone or in combination with other drugs used in chemotherapy. It induces sensitivity of some human cancers toward chemotherapeutical drugs. TSA also exhibits its action on epigenetic modulators involved in cell transformation, and therefore it is considered an epidrug candidate for cancer therapy. Accordingly, this work presents a comprehensive review of the most recent developments in utilizing this natural compound for the prevention, management, and treatment of various diseases, including cancer, along with the multiple mechanisms of action. In addition, this review summarizes the most recent and relevant literature that deals with the use of TSA as a therapeutic agent against various diseases, emphasizing its anticancer potential and the anticancer molecular mechanisms. Moreover, TSA has not been involved in toxicological effects on normal cells. Furthermore, this work highlights the potential utilization of TSA as a complementary or alternative medicine for preventing and treating cancer, alone or in combination with other anticancer drugs.

Natural Bioactive Compounds Targeting Epigenetic Pathways in Cancer: A Review on Alkaloids, Terpenoids, Quinones, and Isothiocyanates.

Cancer is one of the most complex and systemic diseases affecting the health of mankind, causing major deaths with a significant increase. This pathology is caused by several risk factors, of which genetic disturbances constitute the major elements, which not only initiate tumor transformation but also epigenetic disturbances which are linked to it and which can induce transcriptional instability. Indeed, the involvement of epigenetic disturbances in cancer has been the subject of correlations today, in addition to the use of drugs that operate specifically on different epigenetic pathways. Natural molecules, especially those isolated from medicinal plants, have shown anticancer effects linked to mechanisms of action. The objective of this review is to explore the anticancer effects of alkaloids, terpenoids, quinones, and isothiocyanates.

Anticancer mechanisms of phytochemical compounds: focusing on epigenetic targets.

It has recently been proven that epigenetic dysregulation is importantly involved in cell transformation and therefore induces cancerous diseases. The development of molecules called epidrugs, which target specifically different epigenetic modifications to restore cellular memory and therefore the treatment, became a real challenge currently. Currently, bioactive compounds of medicinal plants as epidrugs have been can identified and explored in cancer therapy. Indeed, these molecules can target specifically different epigenetic modulators including DNMT, HDAC, HAT, and HMT. Moreover, some compounds exhibit stochastic epigenetic actions on different pathways regulating cell memory. In this work, pharmacodynamic actions of natural epidrugs belonging to cannabinoids, carotenoids, chalcones, fatty acids, lignans, polysaccharides, saponins, secoiridoids, steroids, tannins, tanshinones, and other chemical classes we reported and highlighted. In this review, the effects of several natural bioactive compounds of epigenetic medications on cancerous diseases were highlighted. Numerous active molecules belonging to different chemical classes such as cannabinoids, carotenoids, fatty acids, lignans, polysaccharides, saponins, secoiridoids, steroids, tannins, and tanshinones are discussed in this review.

Influence of Environmental Factors on Essential Oil Variability in Origanum compactum Benth. Growing Wild in Morocco.

The present study aimed to evaluate the influence of environmental factors on essential oils (EOs) composition of Origanum compactum populations sampled all over the distribution area of the species in Morocco, and to determine the extent of the chemical profiles throughout the geographical distribution of the species. The chemical compositions were submitted to canonical correlation analysis and canonical discriminant analysis that indicated a significant relationship between oil components and some environmental factors. According to their chemical composition and edapho-climatic characteristics, two major groups of populations were differentiated. The first group was composed of samples growing in regions with humid climate, clayey, sandy, and alkaline soils. These samples showed high thymol, α-terpineol, linalool, and carvacryl methyl oxide content. The second group consisted of plants belonging to semi-arid climate, and growing at high altitudes and silty soils. These samples were characterized by high carvacrol, α-thujene, α-terpinene, and myrcene content. However, populations exposed to sub-humid climate, appeared less homogeneous and belong mainly either to the first or second group. A significant correlation between some edaphic factors (pH, K2 O content, soil texture) and the EOs yield of O. compactum plants was evidenced. In spite of the correlation obtained for the oil composition with edapho-climatic factors and the variance explained by the environmental data set, the observed EO diversity might be also genetically determined.

Chemical Polymorphism of Origanum compactum Grown in All Natural Habitats in Morocco.

Origanum compactum L. (Lamiaceae) is one of the most important medicinal species in term of ethnobotany in Morocco. It is considered as a very threatened species as it is heavily exploited. Its domestication remains the most efficient way to safeguard it for future generations. For this purpose, wide evaluation of the existing variability in all over the Moroccan territory is required. The essential oils of 527 individual plants belonging to 88 populations collected from the whole distribution area of the species in Morocco were analyzed by GC/MS. The dominant constituents were carvacrol (0 - 96.3%), thymol (0 - 80.7%), p-cymene (0.2 - 58.6%), γ-terpinene (0 - 35.2%), carvacryl methyl ether (0 - 36.2%), and α-terpineol (0 - 25.8%). While in the Middle Atlas region and the Central Morocco mainly carvacrol type samples were found, much higher chemotypic diversity was encountered within samples from the north part of Morocco (occidental and central Rif regions). The high chemical polymorphism of plants offers a wide range for selection of valuable chemotypes, as a part of breeding and domestication programs of this threatened species.