Anticancer Chemodiversity of Ranunculaceae Medicinal Plants: Molecular Mechanisms and Functions

Abstract

The buttercup family, Ranunculaceae, comprising more than 2,200 species in at least 62 genera, mostly herbs, has long been used in folk medicine and worldwide ethnomedicine since the beginning of human civilization. Various medicinal phytometabolites have been found in Ranunculaceae plants, many of which, such as alkaloids, terpenoids, saponins, and polysaccharides, have shown anti-cancer activities in vitro and in vivo. Most concerns have been raised for two epiphany molecules, the monoterpene thymoquinone and the isoquinoline alkaloid berberine. At least 17 genera have been enriched with anti-cancer phytometabolites. Some Ranunculaceae phytometabolites induce the cell cycle arrest and apoptosis of cancer cells or enhance immune activities, while others inhibit the proliferation, invasion, angiogenesis, and metastasis, or reverse the multi-drug resistance of cancer cells thereby regulating all known hallmarks of cancer. These phytometabolites could exert their anti-cancer activities via multiple signaling pathways. In addition, absorption, distribution, metabolism, and excretion/toxicity properties and structure/activity relationships of some phytometabolites have been revealed assisting in the early drug discovery and development pipelines. However, a comprehensive review of the molecular mechanisms and functions of Ranunculaceae anti-cancer phytometabolites is lacking. Here, we summarize the recent progress of the anti-cancer chemo- and pharmacological diversity of Ranunculaceae medicinal plants, focusing on the emerging molecular machineries and functions of anti-cancer phytometabolites. Gene expression profiling and relevant omics platforms (e.g. genomics, transcriptomics, proteomics, and metabolomics) could reveal differential effects of phytometabolites on the phenotypically heterogeneous cancer cells.

Crosstalk of Multi-Omics Platforms with Plants of Therapeutic Importance

“…The medicinal phytometabolites, such as saponins, alkaloids, terpenoids and polysaccharides, some of which are antitumerogenic, have been identified in Ranunculaceae. The expression profiling of various genes and appropriate transcriptomics platforms have revealed the distinct outcomes of phyto-metabolites in cancerous cells [ 103 ]. The transcriptomic data of Catharanthus roseus (L.) G. Don generates diverse iridoid-based monoterpene indole alkaloids along with anti-cancerous vinblastine [ 104 ].…”

A Natural Isoquinoline Alkaloid With Antitumor Activity: Studies of the Biological Activities of Berberine

“…In human lung cancer A549 cells, berberine increased the expression of E-cadherin protein in a concentration- and time-dependent manner (Li et al, 2018), and significantly downregulated the expression of N -cadherin; these changes inhibited invasion and metastasis. MMPs are a class of important proteins that are involved in that the degradation of the extracellular matrix barrier, which is the first step in tumor cell metastasis (Hao et al, 2017). Studies have shown that berberine inhibits the expression of MMP2 and MMP9 in a time- and concentration-dependent manner.…”

Biological Activities and Phytochemical Screening of Ethanol Extracts From Adonis Paryadrica (Ranunculaceae)

“…The specimens belonging to A. paryadrica were recollected within the scope of a project supported by Ministry of Agriculture and Forestry of the Republic of Turkey. Important biological activities due to their high secondary metabolite contents such as alkaloids, saponins and steroids on the species of the Ranunculaceae have been reported by researchers [9,12]. Furthermore, the family species are included in the group of medicinal and aromatic plants by the same researchers [9,12].…”

“…Important biological activities due to their high secondary metabolite contents such as alkaloids, saponins and steroids on the species of the Ranunculaceae have been reported by researchers [9,12]. Furthermore, the family species are included in the group of medicinal and aromatic plants by the same researchers [9,12]. Members of the Ranunculaceae have a rich content of cardioactive steroids and cardiac glycosides which have been identified as a result of toxic poisoning.…”