Research Articles (Pharmacology)

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  • ItemOpen Access
    Reversal of mitochondrial permeability transition pore and pancreas degeneration by chloroform fraction of Ocimum gratissimum (L.) leaf extract in type 2 diabetic rat model
    (Frontiers Media, 2023) Salemcity, A. J.; Olanlokun, John Oludele; Olowofolahan, A. O.; Olojo, F. O.; Adegoke, Ayodeji Mathias; Olorunsogo, O. O.
    𝗜𝗻𝘁𝗿𝗼𝗱𝘂𝗰𝘁𝗶𝗼𝗻: Unmanaged Diabetes Mellitus (DM) usually results to tissue wastage because of mitochondrial dysfunction. Adverse effects of some drugs used in the management of DM necessitates the search for alternative therapy from plant origin with less or no side effects. Ocimum gratissimum (L.) (OG) has been folklorically used in the management of DM. However, the mechanism used by this plant is not fully understood. This study was designed to investigate the effects of chloroform fraction of OG leaf (CFOG) in the reversal of tissue wastage in DM via inhibition of mitochondrial-mediated cell death in streptozotocin (STZ)-induced diabetic male Wistar rats. 𝗠𝗲𝘁𝗵𝗼𝗱𝘀: Air-dried OG leaves were extracted with methanol and partitioned successively between n-hexane, chloroform, ethylacetate and methanol to obtain their fractions while CFOG was further used because of its activity. Diabetes was induced in fifteen male Wistar rats, previously fed with high fat diet (28 days), via a single intraperitoneal administration of STZ (35 mg/kg). Diabetes was confirmed after 72 h. Another five fed rats were used as the normal control, treated with corn oil (group 1). The diabetic animals were grouped (n = 5) and treated for 28 days as follows: group 2 (diabetic control: DC) received corn oil (10 mL/kg), groups 3 and 4 were administered 400 mg/kg CFOG and 5 mg/kg glibenclamide, respectively. Body weight and Fasting Blood Glucose (FBG) were determined while Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and beta cell (HOMA-β), and pancreatic tissue regenerating potential by CFOG were assessed. Activity-guided purification and characterization of the most active principle in CFOG was done using chromatographic and NMR techniques. The animals were sacrificed after 28 days, blood samples were collected and serum was obtained. Liver mitochondria were isolated and mitochondrial permeability transition (mPT) was investigated by spectrophotometry. 𝗥𝗲𝘀𝘂𝗹𝘁𝘀: CFOG reversed diabetic-induced mPT pore opening, inhibited ATPase activity and lipid peroxidation. CFOG reduced HOMA-IR but enhanced HOMA-β and caused regeneration of pancreatic cells relative to DC. Lupanol was a major metabolite of CFOG. 𝗗𝗶𝘀𝗰𝘂𝘀𝘀𝗶𝗼𝗻: Normoglycemic effect of CFOG, coupled with reversal of mPT, reduced HOMA-IR and improved HOMA-β showed the probable antidiabetic mechanism and tissue regenerating potentials of OG.
  • ItemOpen Access
    The protective roles of citrus flavonoids, naringenin, and naringin on endothelial cell dysfunction in diseases
    (Elsevier, 2023) Adetunji, Joy A.; Fasae, Kehinde D.; Awe, Ayobami I.; Paimo, Oluwatomiwa K.; Adegoke, Ayodeji M.; Akintunde, Jacob K.; Sekhoacha, Mamello P.
    The endothelial cells (ECs) make up the inner lining of blood vessels, acting as a barrier separating the blood and the tissues in several organs. ECs maintain endothelium integrity by controlling the constriction and relaxation of the vasculature, blood fluidity, adhesion, and migration. These actions of ECs are efficiently coordinated via an intricate signaling network connecting receptors, and a wide range of cellular macromolecules. ECs are naturally quiescent i.e.; they are not stimulated and do not proliferate. Upon infection or disease, ECs become activated, and this alteration is pivotal in the pathogenesis of a spectrum of human neurological, cardiovascular, diabetic, cancerous, and viral diseases. Considering the central position that ECs play in disease pathogenesis, therapeutic options have been targeted at improving ECs integrity, assembly, functioning, and health. The dietary intake of flavonoids present in citrus fruits has been associated with a reduced risk of endothelium dysfunction. Naringenin (NGN) and Naringin (NAR), major flavonoids in grapefruit, tomatoes, and oranges possess anti-inflammatory, antioxidant properties, and cell survival potentials, which improve the health of the vascular endothelium. In this review, we provide a comprehensive summary and present the advances in understanding of the mechanisms through which NGN and NAR modulate the biomarkers of vascular dysfunction and protect the endothelium against unresolved inflammation, oxidative stress, atherosclerosis, and angiogenesis. We also provide perspectives and suggest further studies that will help assess the efficacy of citrus flavonoids in the therapeutics of human vascular diseases.