The phytochemical, biological, and medicinal attributes of phytoecdysteroids: An updated review

Abstract

The phytoecdysteroids (PEs) comprise a large group of biologically-active plant steroids, which have structures similar to those of insect-molting hormones. PEs are distributed in plants as secondary metabolites that offer protection against phytophagus (plant-eating) insects. When insects consume the plants containing these chemicals, they promptly molt and undergo metabolic destruction; the insects eventually die. Chemically, ecdysteroids are a group of polyhydroxylated ketosteroids that are structurally similar to androgens. The carbon skeleton of ecdysteroids is termed as cyclopentanoperhydro-phenanthrene with a β-side chain at carbon-17. The essential characteristics of ecdysteroids are a cis-(5β-H) junction of rings A and B, a 7-en-6-one chromophore, and a trans-(14α-OH) junction of rings C and D. Plants only synthesize PEs from mevalonic acid in the mevalonate pathway of the plant cell using acetyl-CoA as a precursor; the most common PE is 20-hydroxyecdysone. So far, over 400 PEs have been identified and reported, and a compilation of 166 PEs originating from 1998 has been previously reviewed. In the present review, we have summarized 212 new PEs reported between 1999 and 2019. We have also critically analyzed the biological, pharmacological, and medicinal properties of PEs to understand the full impact of these phytoconstituents in health and disease.

Keywords: Anti-inflammatory; Anticancer activity; Antidiabetic; Antimicrobial; Antioxidant; Phytoecdysteroids; Secondary metabolites.

Graphical abstract

Figure 1

Structures of 20-hydroxyecdysone (1), ponasterones A (2), B (3) and C (4).

Figure 2

Structures of reported new phytoecdysteroids (5–37) from Amaranthaceae family.

Figure 3

Structures of reported new phytoecdysteroids (38–87) from Asteraceae family.

Figure 4

Structures of reported new phytoecdysteroids (88–92) from Blechnaceae family.

Figure 5

Structures of reported new phytoecdysteroids (93–128) from Caryophyllaceae family.

Figure 6

Structures of reported new phytoecdysteroids (129–151) from Clavicipitaceae, Commelinaceae, Dioscoreaceae, and Gleicheniaceae families.

Figure 7

Structures of reported new phytoecdysteroids (152–180) from Lamiaceae family.

Figure 8

Structures of reported new phytoecdysteroids (181–216) from Liliaceae, Limnanthaceae, Lygodiaceae, Malvaceae, Menispermaceae, Polypodiaceae, Polyporaceae, Rhodomelaceae, and Taxaceae families.

Figure 9

Probable biosynthetic route of 20-hydroxyecdysone in plants.

Figure 10

Overview of anti-inflammatory effects of phytoecdysteroids. Phytoecdysteroids tend to interfere with the membrane fluidity which leads to cell sensitization and modulate various cellular signaling processes in immunomodulation and inflammation. This especially involves the inhibition of NF-κB, COX-2, MDA, MAPKs and Akt, and activation of HO-1, Nrf2, eNOS and SOD. Akt, protein kinase B; COX-2, cyclooxygenase-2; eNOS, endothelial nitric oxide synthase; ET, endothelin; HO-1, hemaoxygenase-1; MAPKs, mitogen-activated protein kinases; MDA, malondialdehyde; NF-κB, nuclear factor-κB; NO, nitric oxide; Nrf2, nuclear factor erythroid 2-related factor 2; SOD, superoxide dismutase; TXA2, thromboxane A2.

Figure 11

Tissue differentiation and growth modulatory activities of phytoecdysteroids. Calonysterone specifically alteres tissue differentiation and growth modulation, and affects cell proliferation and survival signalling mechanisms. Akt, protein kinase B.

Figure 12

Proposed mechanism of the anticancer effects of phytoecdysteroids through induction of cell death. Phytoecdysteroids interact through the ABCB1 transmembrane protein and activates mitochondrial apoptosis pathway as well as it suppresses oxidative stress and causes cell cycle arrest. These collectively lead to inhibition of cell proliferation and cell death. ABCB1, transmembrane efflux transporter; CAT, catalase; PARP, poly(ADP-ribose) polymerase; POX, peroxidase; ROS, reactive oxygen species; SOD, superoxide dismutase.

Figure 13

Summary of various biological and pharmacological effects of ecdysteroids.