Computational and Biological Comparisons of Plant Steroids as Modulators of Inflammation through Interacting with Glucocorticoid Receptor

Abstract

Despite the usefulness of glucocorticoids, they may cause hazardous side effects that limit their use. Searching for compounds that are as equally efficient as glucocorticoids, but with less side effects, the current study compared plant steroids, namely, glycyrrhetinic acid, guggulsterone, boswellic acid, withaferin A, and diosgenin with the classical glucocorticoid, fluticasone. This was approached both in silico using molecular docking against glucocorticoid receptor (GR) and in vivo in two different animal models. All tested compounds interacted with GR, but only boswellic acid and withaferin A showed docking results comparable to fluticasone, as well as similar in vivo anti-inflammatory effects, by significantly decreasing serum levels of interleukin-6 and tumor necrosis factor-α in cotton pellet-induced granuloma in rats. In addition, both compounds significantly decreased the percent of change in ear weight in croton oil-induced ear edema in mice and the granuloma weight in cotton pellet-induced granuloma in rats, to levels comparable to that of fluticasone. Both boswellic acid and withaferin A had no effect on adrenal index, but only withaferin A significantly increased the thymus index. In conclusion, boswellic acid may have comparable anti-inflammatory effects to fluticasone with fewer side effects.

Carbenoxolone and 18β‐glycyrrhetinic acid inhibit inositol 1,4,5‐trisphosphate‐mediated endothelial cell calcium signalling and depolarise mitochondria

“…There are several reports of “off‐target” effects which may account for some of the effects of 18βGA and CBX on cell–cell communication. Glycyrrhetinic acids bind strongly to mineralocorticoid and glucocorticoid receptors (Armanini, Karbowiak, & Funder, 1983; Kratschmar et al, 2011), inhibit 11β‐hydroxysteroid dehydrogenase and act in anti‐inflammatory roles through these pathways (Morsy et al, 2019). CBX also shows high affinity for the mineralocorticoid receptor (Armanini, Karbowiak, Krozowski, Funder, & Adam, 1982).…”

The Beneficial Effect of Boswellic Acid on Bone Metabolism and Possible Mechanisms of Action in Experimental Osteoporosis

“…A review of literature signifies that inhibition of NF-κB expression leads to a decline in RANKL expression, resulting in osteoblast differentiation and consequently reducing bone loss [ 17 , 18 ]. Previous studies reported that boswellic acid has a positive impact in the treatment of chronic inflammatory diseases by different mechanisms of action [ 19 , 20 ]. In addition, the anti-inflammatory actions of AKBA are due to the inhibition of leukotriene synthesis and a decrease in the formation of proinflammatory cytokines, which includes interleukin (IL)-1, IL-2, IL-6, interferon-γ, TNF-α, and NF-κB, which are primarily responsible for destroying bone cartilage.…”

Utilizing methylglyoxal and D-lactate in urine to evaluate saikosaponin C treatment in mice with accelerated nephrotoxic serum nephritis

“…In this study, we observed that SSC may ameliorate NTS nephritis in mice as reported by Chen et al ., and the efficacy is probably due to the steroid-like structure of SSC [ 13 ]. It was previously noted that the phytosterols with triterpene structure may alleviate inflammation via activation of the glucocorticoid receptor (GR) [ 54 ]. According to a recent study of aristolochic acid nephropathy, prednisolone may alleviate renal damage and fibrosis and inhibit glycolysis [ 39 ].…”