Phytochemical Study and Antiglioblastoma Activity Assessment of Plectranthus hadiensis (Forssk.) Schweinf. ex Sprenger var. hadiensis Stems

Abstract

Glioblastoma (GB) is the most malignant form of primary astrocytoma, accounting for more than 60% of all brain tumors in adults. Nowadays, due to the development of multidrug resistance causing relapses to the current treatments and the development of severe side effects resulting in reduced survival rates, new therapeutic approaches are needed. The genus Plectranthus belongs to the Lamiaceae family and is known to be rich in abietane-type diterpenes, which possess antitumor activity. Specifically, P. hadiensis (Forssk.) Schweinf. ex Sprenger has been documented for the use against brain tumors. Therefore, the aim of this work was to perform the bioguided isolation of compounds from the acetonic extract of P. hadiensis stems and to investigate the in vitro antiglioblastoma activity of the extract and its isolated constituents. After extraction, six fractions were obtained from the acetonic extract of P. hadiensis stems. In a preliminary biological screening, the fractions V and III showed the highest antioxidant and antimicrobial activities. None of the fractions were toxic in the Artemia salina assay. We obtained different abietane-type diterpenes such as 7α-acetoxy-6β-hydroxyroyleanone (Roy) and 6β,7β-dihydroxyroyleanone (DiRoy), which was also in agreement with the HPLC-DAD profile of the extract. Furthermore, the antiproliferative activity was assessed in a glioma tumor cell line panel by the Alamar blue assay. After 48 h treatment, Roy exerted strong antiproliferative/cytotoxic effects against tumor cells with low IC50 values among the different cell lines. Finally, we synthesized a new fluorescence derivative in this study to evaluate the biodistribution of Roy. The uptake of BODIPY-7α-acetoxy-6β-hydroxyroyleanone by GB cells was associated with increased intracellular fluorescence, supporting the antiproliferative effects of Roy. In conclusion, Roy is a promising natural compound that may serve as a lead compound for further derivatization to develop future therapeutic strategies against GB.

Improving Foodborne Pathogen Control Using Green Nanosized Emulsions of Plectranthus hadiensis Phytochemicals

“…All PHT extracts showed antimicrobial activity against both Gram-positive and Gramnegative bacteria, which differs from previous reports [10,37,44,45] where PHT extracts exhibited antimicrobial activity only against Gram-positive bacteria such as Staphylococcus aureus, Bacillus subtilis, Micrococcus flavus, and Enterococcus faecalis. However, Kotagiri, Shaik, and Kolluru [8], as well as Sripathi and Ravi [46], reported that in addition to having antimicrobial activity against Gram-positive bacteria, PHT extracts also showed activity against Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa.…”

“…tomentosus (PHT) or "VapoRub TM plant", as it is commonly called in Mexico, it has been used to treat various digestive, respiratory, and skin problems, such as dysentery, 2 of 19 vomiting, nausea, diarrhea, fever, sore throat, common cold, asthma, inflammations, and smallpox, because it is a rich source of bioactive phytochemicals, especially terpenoids. The juice from the leaves and stems mixed with honey treats diarrhea, while its infusions treat cough [6][7][8][9][10].…”

Essential Oils from Côa Valley Lamiaceae Species: Cytotoxicity and Antiproliferative Effect on Glioblastoma Cells

“…According to the World Health Organization (WHO), this adult-type diffuse glioma is classified as a grade IV tumor (highly malignancy level) [ 1 ]. Despite the advances in the clinic to improve patient survival, the overall average survival rate for GB is only 15–21 months after diagnosis, with just a 5% probability of survival in the 5 years post-diagnosis [ 2 , 3 , 4 ]. These numbers are not surprising, being explained by the late diagnosis and poor prognosis of GB.…”

“…These numbers are not surprising, being explained by the late diagnosis and poor prognosis of GB. Thus, to hinder this situation, the current first-line treatment available for GB includes maximal surgical resection followed by concomitant cycles of chemoradiotherapy and adjuvant chemotherapy (temozolomide (TMZ)) [ 3 , 4 , 5 , 6 , 7 ]. Although, these treatments have several limitations, such as incomplete surgical resection or development of multidrug resistance (MDR), that provoke patient relapse [ 8 ].…”

“…The well-known therapeutic significance attributed to plants usually resides in the secondary metabolites they produce. These metabolites represent an important source of bioactive molecules in the process of discovery and development of new pharmacologically active compounds, particularly for cancer therapy [ 3 , 10 , 11 ]. In fact, several chemotherapy agents currently in clinical use derived from plants or were inspired in the chemical structure of plant-extracted compounds [ 12 , 13 ].…”