Phytomodulatory proteins isolated from Calotropis procera latex promote glycemic control by improving hepatic mitochondrial function in HepG2 cells

Abstract

The medicinal uses of Calotropis procera are diverse, yet some of them are based on effects that still lack scientific support. Control of diabetes is one of them. Recently, latex proteins from C. procera latex (LP) have been shown to promote in vivo glycemic control by the inhibition of hepatic glucose production via AMP-activated protein kinase (AMPK). Glycemic control has been attributed to an isolated fraction of LP (CpPII), which is composed of cysteine peptidases (95%) and osmotin (5%) isoforms. Those proteins are extensively characterized in terms of chemistry, biochemistry and structural aspects. Furthermore, we evaluated some aspects of the mitochondrial function and cellular mechanisms involved in CpPII activity. The effect of CpPII on glycemic control was evaluated in fasting mice by glycemic curve and glucose and pyruvate tolerance tests. HepG2 cells was treated with CpPII, and cell viability, oxygen consumption, PPAR activity, production of lactate and reactive oxygen species, mitochondrial density and protein and gene expression were analyzed. CpPII reduced fasting glycemia, improved glucose tolerance and inhibited hepatic glucose production in control animals. Additionally, CpPII increased the consumption of ATP-linked oxygen and mitochondrial uncoupling, reduced lactate concentration, increased protein expression of mitochondrial complexes I, III and V, and activity of peroxisome-proliferator-responsive elements (PPRE), reduced the presence of reactive oxygen species (ROS) and increased mitochondrial density in HepG2 cells by activation of AMPK/PPAR. Our findings strongly support the medicinal use of the plant and suggest that CpPII is a potential therapy for prevention and/or treatment of type-2 diabetes. A common epitope sequence shared among the proteases and osmotin is possibly the responsible for the beneficial effects of CpPII.

Radical oxygen species: an important breakthrough point for botanical drugs to regulate oxidative stress and treat the disorder of glycolipid metabolism

“…For example, latex protein from Calotropis procera increased the expression of mitochondrial complexes I, III, and V; improved glucose tolerance; and inhibited hepatic glucose production in mice. This makes it a potential agent for the treatment of type 2 DM (De Oliveira et al, 2021).…”

Tap the sap – investigation of latex-bearing plants in the search of potential anticancer biopharmaceuticals

“…The aforementioned compound has given rise to a hemi-synthetic cardenolide, UNBS1450, which has been shown to have an antiproliferative effect and induce cell death through its inhibition of sodium pumps. (Mascolo et al, 1988;Pant and Chaturvedi, 1989;Qasim Khan and Malik, 1989;Van Quaquebeke et al, 2005;Juncker et al, 2009;Mohamed et al, 2011;Cornelius et al, 2013;Jucáet al, 2013;Viana et al, 2017;Oliveira et al, 2021) This inhibition is presumed to occur due to its double-linked sugar moiety and its steroid core structure. The UNBS1450 had also shown an inhibitory effect on A549, as well as human astrocytoma (U373-MG) cells, through interference in the NF-kB signaling pathway and not enabling daughter cells division, respectively.…”

“…A human apoptosis and cell stress proteome array showed the downregulation of a majority of proteins in GAMG cell lines (Table 3) after euphol administration, as well as an increase in LC3-II expression and the development of fractional volume of acidic vesicular organelles (AVOs), which suggests the involvement of autophagy cell death related processes (Silva et al, 2019). An in vivo assay testing the activity of euphol from E. tirucalli had been used to evaluate In vitro (HepG2) (Oliveira et al, 2021) Increased expression of beclin-1 and LC3 autophagy markers UNBS1450, a hemi-synthetic derivative of 2'-Oxovuruscharin…”