An Evaluation of the Novel Biological Properties of Diterpenes Isolated from Plectranthus ornatus Codd. In Vitro and In Silico

Abstract

Plectranthus ornatus Codd, the genus Plectranthus of the Lamiaceae family, has been used as traditional medicine in Africa, India and Australia. Pharmacological studies show the use of this plant to treat digestive problems. In turn, leaves were used for their antibiotic properties in some regions of Brazil to treat skin infections. The present study examines the anti-inflammatory, antioxidant and cytotoxic effects of the halimane and labdane diterpenes (11R*,13E)-11-acetoxyhalima-5,13-dien-15-oic acid (HAL) and 1α,6β-diacetoxy-8α,13R*-epoxy-14-labden-11-one (PLEC) and the forskolin-like 1:1 mixture of 1,6-di-O-acetylforskolin and 1,6-di-O-acetyl-9-deoxyforskolin (MRC) isolated from P. ornatus on lung (A549) and leukemia (CCRF-CEM) cancer cell lines, and on normal human retinal pigment epithelial (ARPE-19) cell line in vitro. Additionally, molecular docking and computational approaches were used. ADMET properties were analysed through SwissADME and proTox-II—Prediction. The results indicate that all tested compounds significantly reduced the viability of the cancer cells and demonstrated no cytotoxic effects against the non-neoplastic cell line. The apoptosis indicators showed increased ROS levels for both the tested A549 and CCRF-CEM cancer cell lines after treatment. Furthermore, computational studies found HAL to exhibit moderate antioxidant activity. In addition, selected compounds changed mitochondrial membrane potential (MMP), and increased DNA damage and mitochondrial copy number for the CCRF-CEM cancer cell line; they also demonstrated anti-inflammatory effects on the ARPE-19 normal cell line upon lipopolysaccharide (LPS) treatment, which was associated with the modulation of IL-6, IL-8, TNF-α and GM-CSF genes expression. Docking studies gave indication about the lowest binding energy for 1,6-di-O-acetylforskolin docked into IL-6, TNF-α and GM-CSF, and 1,6-di-O-acetyl-9-deoxyforskolin docked into IL-8. The ADMET studies showed drug-likeness properties for the studied compounds. Thus, halimane and labdane diterpenes isolated from P. ornatus appear to offer biological potential; however, further research is necessary to understand their interactions and beneficial properties.

Plectranthus: From Traditional Medicine to Brain Tumor Therapy With Diterpenes

“…Roy demonstrated strong antiproliferative and cytotoxic effects against tumor cells, with low IC50 values in various cell lines. Additionally, a new fluorescence derivative, BODIPY-Roy, confirmed the increased intracellular fluorescence associated with Roy's antiproliferative activity, suggesting its potential as a basis for the development of new therapeutic strategies against glioblastoma [1,2].…”

“…The compound displayed cytotoxic activity against glioblastoma, inducing apoptosis through the intrinsic mitochondrial pathway and disrupting the G2/M cell cycle. Its antitumor efficacy surpassed that of the first-line treatment temozolomide in glioblastoma and showed potential against triple-negative breast cancer, reducing cell viability, inducing İD apoptosis, and inhibiting cell migration and invasion, indicating potential antimetastatic effects [1].…”

Biodynamic Substrate for the Optimization of Biomass and Constitution of Metabolites of Plectranthus Ornatus

“…Pharmacological studies of P. ornatus have shown its antibiotic, anti-in ammatory, antioxidant, and cytotoxic effects on leukemia and lung cancer cells (Sitarek et al, 2022). The P. ornatus extract has also shown antioxidant capacity, mainly associated with compounds such as rosmarinic, caffeic, and o-hydroxycinnamic acids (Medrado et al, 2016).…”

Advances in Plants-Derived Bioactives for Cancer Treatment

“…In another study, the anticancer activity of a natural compound, in this case, daphnoretin, was tested by Huang et al [ 9 ] in human chronic myeloid leukemia cells. As their main finding, the authors observed that daphnoretin intervened at the level of the cell cycle, inhibiting tumor growth and also inducing megakaryocytic differentiation.…”