A Review on Worldwide Ephedra History and Story: From Fossils to Natural Products Mass Spectroscopy Characterization and Biopharmacotherapy Potential

Abstract

Growing worldwide, the genus Ephedra (family Ephedraceae) had a medicinal, ecological, and economic value. The extraordinary morphological diversity suggests that Ephedra was survivor of an ancient group, and its antiquity is also supported by fossil data. It has recently been suggested that Ephedra appeared 8–32 million years ago, and a few megafossils document its presence in the Early Cretaceous. Recently, the high analytical power provided by the new mass spectrometry (MS) instruments is making the characterization of Ephedra metabolites more feasible, such as ephedrine series. In this regard, the chemical compounds isolated from crude extracts, fractions, and few isolated compounds of Ephedra species were characterized by MS-based techniques (LC-MS, LC-ESI-MS, HPLC-PDA-ESI/MS, LC-DAD-ESI/MSn, LC/Orbitrap MS, etc.). Moreover, we carry out an exhaustive review of the scientific literature on biomedicine and pharmacotherapy (anticancer, antiproliferative, anti-inflammatory, antidiabetic, antihyperlipidemic, antiarthritic, and anti-influenza activities; proapoptotic and cytotoxic potential; and so on). Equally, antimicrobial and antioxidant activities were discussed. This review is focused on all these topics, along with current studies published in the last 5 years (2015–2019) providing in-depth information for readers.

A Review of the Ephedra genus: Distribution, Ecology, Ethnobotany, Phytochemistry and Pharmacological Properties

“…Secondary metabolites isolated from soluble extracts in organic solvents obtained from both aerial parts and roots of Ephedra plants are represented by 26 alkaloids, mainly ones with an ephedrine-type framework (compounds 1 – 26 ); 75 phenolic compounds, which include aromatic compounds, flavonoids, lignans and proanthocyanidins (compounds 27 – 99 ); and seven amino acid derivatives (compounds 100 – 106 ). Furthermore, in the essential oils of these species, 98 volatile organic compounds (VOCs) were obtained by hydrodistillation and about 70 compounds were obtained by extraction with supercritical CO 2 [ 46 , 47 , 48 , 49 ]. Two additional aspects that illustrate the chemical diversity of Ephedra genus are the chemotaxonomy approaches and the use of ephedrine-type alkaloids as building blocks during organic synthesis (eg., compounds 107 – 124 ) [ 50 , 51 , 52 , 53 , 54 , 55 ].…”

Paleomedicine and the Evolutionary Context of Medicinal Plant Use

“…Near the graves at Shanidar, clusters of pollen from several plants, including a member of the genus Ephedra , Ephedraceae, identified as having significant medicinal properties, led to the suggestion that these had been deliberately placed (Solecki 1975 ; Leroi-Gourhan 1975 ); however, whether the plants were intentionally deposited is doubtful as it could be due to rodent activity (Sommer 1999 ). Of the bioactive alkaloids found in Ephedra (at concentrations of 0.02–3.4%), the most common is ephedrine ( 1 ); these ephedrine-type alkaloids are responsible for the stimulant and thermogenic effects of the crude drug, which also included antioxidant and antimicrobial properties (Elhadef et al 2020 ).…”

In search of an ideal drug for safer treatment of obesity: The false promise of pseudoephedrine

“…In particular, Ephedra sinica , a member of the Ephedraceae family, is the most commonly used in preparations and extracts. Ephedra includes several sympathomimetic substances, such as ephedrine, pseudoephedrine, nor-ephedrine, methyl-ephedrine, and methyl-pseudoephedrine, all substances with molecular structures related to catecholamines and amphetamines [ 52 ]. The alkaloid content of Ephedra species is highly variable, depending upon the type, the parts of the plant used and the method of extraction, the most represented being ephedrine and its stereoisomer pseudoephedrine (Fig.…”