Methanol fraction of Calliandra portoricensis root bark activates caspases via alteration in mitochondrial viability in vivo

Introduction: Dysregulated apoptosis is associated with a number of disease conditions. Traditionally, Calliandra portoricensis is used in the management of prostate enlargement. This study investigates the in vivo effect of potent methanol fraction of C. portoricensis (MFCP) on mitochondrial permeability transition (mPT) pore, an important pharmacological target in treatment of various diseases, and examines the toxicities associated with its oral administration. Methods: Forty-two male Wistar strain rats (70-80 g) were divided into 6 groups of 7 animals each. Each group was orally administered 25, 50, 100, 200, 400 mg/kg MFCP and the control group received distilled water for 21 and 30 days, respectively. mPT, assay for serum enzymes and hematological parameters were assessed spectrophotometrically while activation of caspases 3 and 9 was done by ELISA technique. Histological assessment of vital organs (liver, kidney, prostate) was carried out according to standard procedures. Results: There were no significant effects on mPT pore at all doses administered after 21 days of oral administration. However, after 30 days of administration, MFCP induced mPT pore opening at doses 100 and 200 mg/kg with induction folds of 2.6 and 3.3, respectively while there was no induction of mPT pore opening at lower doses of 25 mg/kg and 50 mg/kg. Furthermore, significant (P < 0.05) increases in serum enzymes (ALT, AST) were observed at all doses administered when compared with control after 30 days of oral administration. Cell counts (Hb, PCV, RBC, WBC) were adversely affected at the highest dose (200 mg/kg) compared with control and other treated groups (25, 50 and 100 mg/kg) after 30 days of administration. Similarly, activation of caspases 9 and 3 were observed in rat liver homogenate at high doses of the fraction while histological evaluation showed degeneration and distortion of organs at the highest dose. Conclusion: MFCP contains phytochemicals that elicit the opening of the pore and induction of mitochondrial-mediated apoptosis. This would be relevant in treatment of degenerative diseases that results from down-regulation of apoptosis. However, caution should be exercised in using high doses of the plant

In vitro antiproliferative, anti-inflammatory effects and molecular docking studies of natural compounds isolated from Sarcocephalus pobeguinii (Hua ex Pobég)

DATA AVAILABILITY STATEMENT : The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.BACKGROUND : Sarcocephalus pobeguinii (Hua ex Pobég) is used in folk medicine to treat oxidative-stress related diseases, thereby warranting the investigation of its anticancer and anti-inflammatory properties. In our previous study, the leaf extract of S. pobeguinii induced significant cytotoxic effect against several cancerous cells with high selectivity indexes towards non-cancerous cells. AIM : The current study aims to isolate natural compounds from S. pobeguinii, and to evaluate their cytotoxicity, selectivity and anti-inflammatory effects as well as searching for potential target proteins of bioactive compounds. METHODS : Natural compounds were isolated from leaf, fruit and bark extracts of S. pobeguinii and their chemical structures were elucidated using appropriate spectroscopic methods. The antiproliferative effect of isolated compounds was determined on four human cancerous cells (MCF-7, HepG2, Caco-2 and A549 cells) and non-cancerous Vero cells. Additionally, the anti-inflammatory activity of these compounds was determined by evaluating the nitric oxide (NO) production inhibitory potential and the 15-lipoxygenase (15-LOX) inhibitory activity. Furthermore, molecular docking studies were carried out on six putative target proteins found in common signaling pathways of inflammation and cancer. RESULTS : Hederagenin (2), quinovic acid 3-O-[α-D-quinovopyranoside] (6) and quinovic acid 3-O-[β-D-quinovopyranoside] (9) exhibited significant cytotoxic effect against all cancerous cells, and they induced apoptosis in MCF-7 cells by increasing caspase-3/-7 activity. (6) showed the highest efficacy against all cancerous cells with poor selectivity (except for A549 cells) towards noncancerous Vero cells; while (2) showed the highest selectivity warranting its potential safety as a chemotherapeutic agent. Moreover, (6) and (9) significantly inhibited NO production in LPS-stimulated RAW 264.7 cells which could mainly be attributed to their high cytotoxic effect. Besides, the mixture nauclealatifoline G and naucleofficine D (1), hederagenin (2) and chletric acid (3) were active against 15-LOX as compared to quercetin. Docking results showed that JAK2 and COX-2, with the highest binding scores, are the potential molecular targets involved in the antiproliferative and anti-inflammatory effects of bioactive compounds. CONCLUSION : Overall, hederagenin (2), which selectively killed cancer cells with additional anti-inflammatory effect, is the most prominent lead compound which may be further investigated as a drug candidate to tackle cancer progression.The Central University of Technology operational expenses and the National Research Foundation (NRF), South Africa. The APC was funded by the Central University of Technology research expenses (TM).http://www.frontiersin.org/Pharmacologyam2024Paraclinical SciencesSDG-03:Good heatlh and well-bein

NaHCO3 treatment potentiates the nutritional qualities and androgenic capabilities of bambara (Vigna subterranean L. Verdc) groundnut seeds

Bambara groundnut (Vigna subterranean L. Verdc) is a legume crop cultivated by few indigenous subsistence farmers in sub-Saharan Africa. Using established procedures, we investigated the effects of alkaline treatment towards improving the nutritional qualities of these groundnut seeds, and also in enhance the hematological and androgenic capabilities in 6 groups of male Wistar rats fed for 28 days with varied proportions at 0, 10, 30, 50, 70, and 90% of NaHCO3 -treated seeds mixed with basal diet. There were significant increases in several micro- and macro- nutrients and hematological (hemoglobin, packed cell volume, red blood cells, white blood cells, and platelets) and androgenic (testosterone, luteinizing hormone and follicle-stimulating hormone) indicators, when compared to the control group (0%). More importantly, the 70 and 90% fed groups showed significant reduction in the number of abnormal/dead sperm cells with improved sperm cell qualities, in terms of pH, minerals and vitamins. NaHCO3 treatment of Bambara groundnut seeds may therefore provide additional enhancement of the nutritional values, and the consumption could improve vitality and virility. Thus, it will be imperative if this is applied towards formulation of functional foods that can be useful in addressing the associated health challenges and/or malnutrition in developing countries