Bioactivity Profile of the Diterpene Isosteviol and its Derivatives

Abstract

Steviosides, rebaudiosides and their analogues constitute a major class of naturally occurring biologically active diterpene compounds. The wide spectrum of pharmacological activity of this group of compounds has developed an interest among medicinal chemists to synthesize, purify, and analyze more selective and potent isosteviol derivatives. It has potential biological applications and improves the field of medicinal chemistry by designing novel drugs with the ability to cope against resistance developing diseases. The outstanding advancement in the design and synthesis of isosteviol and its derivative has proved its effectiveness and importance in the field of medicinal chemical research. The present review is an effort to integrate recently developed novel drugs syntheses from isosteviol and potentially active pharmacological importance of the isosteviol derivatives covering the recent advances.

Terpenoids as Potential Geroprotectors

“…Steviol glycosides do not cause acute and subacute toxicity, allergic reactions, and they are not teratogenic, mutagenic, and carcinogenic substances. Their safety has been confirmed in numerous toxicological studies [ 187 , 188 ]. A few examples of side effects of some diterpenes are described.…”

“…Stevia rebaudiana leaf extract has an antidiabetic effect by lowering blood glucose levels in patients with type 2 diabetes [ 215 ]. Isosteviol exhibits anti-inflammatory, antihypertensive activity, regulates blood lipids, is an immunomodulator, inhibits DNA polymerase and DNA topoisomerase, having anti-tumor, antioxidant, and anti-tuberculosis effects [ 187 ]. Stevioside and steviol affect β-cells and stimulate insulin secretion in mice and rats [ 216 , 217 , 218 ].…”

“…Stevioside and steviol affect β-cells and stimulate insulin secretion in mice and rats [ 216 , 217 , 218 ]. Steviol glycosides can lower blood pressure by modulating calcium and potassium channels, and repeated administration of stevioside in both normal and hypertensive mice led to an increase in glomerular filtration and renal blood flow [ 187 , 219 ]. Stevioside has an antihyperglycemic and hypotensive effect [ 217 ].…”

Stevia: limiting cholesterol synthesis in Hep-G2 cells

“…Stevia rebaudiana bertoni, generally known as Stevia is a small perennial herbaceous plant famously utilized as a sugar substitute due to its non-toxic and non-caloric characteristics (Kaur et al, 2014;Sharma et al, 2017;Saniah and Samsiah, 2012). Up to date, there are approximately 230 variations of stevia species available but only S. rebaudiana and S. phlebophylla are producing glycosides (Ullah et al, 2019). Stevia is native to South America and belongs to the Asteraceae family grows in sandy soils (Siddique et al, 2012;Shukla et al, 2009).…”

“…Stevia was also reported to play a role as antioxidant, renal protective, anti-tumorigenic, antiinflammatory, reduced atherosclerosis, and promote wound healing (Shivanna et al, 2013;Chen et al, 2018;Greeraert et al, 2010;Das, 2013). Substitution of normal sucrose with stevia is highly recommended for Type-2 diabetes as it does not induce glycemic response due to the inability of humans to metabolize ingested steviol glycosides (Ullah et al, 2019;Geuns et al, 2007). Prolonged consumption has shown no serious effects, which prove that stevia is non-toxic, noncarcinogenic and non-genotoxic to mammals (Koyama et al, 2003).…”