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ETHNOPHARMACOLOGICAL RELEVANCE: Plasmodium resistance to antimalarial drugs raises the urgent need to seek for alternative treatments. Aqueous extract of Hibiscus asper leaves is currently used in malaria management but remains less documented. AIM OF THE STUDY: The study aims to evaluate antimalarial effects of the aqueous extract of Hibiscus asper. UHPLC/MS, was used to identify some likely compounds present in the plant that were thereafter docked to some malaria parasite proteins. STUDY DESIGN: In vitro anti-plasmodium and antioxidant, UHPLC/Ms analysis, in vivo antimalarial of the plant extract, and in silico molecular docking prediction of some identified compounds were performed to investigate the pharmacological effects of H. asper. MATERIAL AND METHODS: The in vitro antiplasmodial activity of the extract was carried out on Plasmodium falciparum strains using SYBR-green dye; then, the curative antimalarial activity was conducted on Plasmodium berghei NK65-infected male Wistar rats. The UHPLC/MS analysis was used to identify plant compounds, followed by interactions (docking affinity) between some compounds and parasitic enzymes such as P. falciparum purine nucleoside phosphorylase (2BSX) and 6-phosphogluconate dehydrogenase (6FQY) to explore potential mechanisms of action at the molecular level. RESULTS: No hemolysis effect of the extract was observed at concentrations up to 100 mg/mL. In vitro test of the aqueous leaves extract of H. asper showed inhibitory activity against P. falciparum Dd2 and 3D7 strains with IC50 values of 19.75 and 21.97 µg/mL, respectively. The curative antimalarial test of the H. asper extract in infected rats exhibited significant inhibition of the parasite growth (p < 0.001) with inhibition percentage of 95.11%, 97.68% and 95.59% at all the doses (50, 100 and 200 mg/kg) respectively. The extract corrected major physiological alterations such as liver and kidney impairments, oxidative stress and architectural disorganization in liver, spleen and kidneys tissues. The UHPLC/MS analysis identified 7 compounds, namely chlorogenic acid, azulene, quercetin, rhodine, 1-ethyl-2,4-dimethyl benzene and phthalan. Out of seven compounds identified in the extract quercetin and phthalan showed higher in silico inhibitory activity against P. falciparum purine nucleoside phosphorylase and Plasmodium falciparum 6-phosphosgluconate dehydrogenase parasite enzymes. CONCLUSION: These findings indicate that H. asper could be a promising complementary medicine to manage malaria. Meanwhile, the affinity of annoted compounds with these enzymes should be further confirmed.
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Diabetes-associated cognitive dysfunction is linked to chronic hyperglycemia, oxidative stress, inflammation, cholinergic dysfunction, and neuronal degeneration. We investigated the antidiabetic and neuroprotective activity of a mixture of Sclerocarya birrea, Nauclea latifolia, and Piper longum (SNP) in type 2 diabetic (T2D) rat model-induced memory impairment. Fructose (10%) and streptozotocin (35 mg/kg) were used to induce T2D in male Wistar rats. Diabetic animals received distilled water, metformin (200 mg/kg), or SNP mixture (75, 150, or 300 mg/kg). HPLC-MS profiling of the mixture was performed. Behavioral testing was conducted using the Y-maze, NORT, and Morris water mazes to assess learning and memory. Biochemical markers were evaluated, including carbohydrate metabolism, oxidative/nitrative stress, pro-inflammatory markers, and acetylcholinesterase activity. Histopathological examination of the pancreas and hippocampus was also performed. Fructose/STZ administration resulted in T2D, impaired short- and long-term memory, significantly increased oxidative/nitrative stress, pro-inflammatory cytokine levels, acetylcholinesterase activity (AChE), hippocampal neuronal loss and degeneration in CA1 and CA3 subfields, and neuronal vacuolation in DG. SNP mixture at 150 and 300 mg/kg significantly improved blood glucose and memory function in diabetic rats. The mixture reduced oxidative/nitrative stress and increased endogenous antioxidant levels. It also reduced serum IL-1ß, INF-γ and TNF-α levels and ameliorated AChE activity. Histologically, SNP protected hippocampus neurons against T2D-induced neuronal necrosis and degeneration. We conclude that the aqueous extract of SNP mixture has antidiabetic and neuroprotective activities thanks to active metabolites identified in the plant mixture, which consequently normalized blood glucose, protected hippocampus neurons, and improved memory function in diabetic rats.
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Anacardiaceae , Disfunción Cognitiva , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Rubiaceae , Ratas , Animales , Ratas Wistar , Acetilcolinesterasa/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/inducido químicamente , Glucemia , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/metabolismo , Hipoglucemiantes/efectos adversos , Estrés Oxidativo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Anacardiaceae/metabolismo , Rubiaceae/metabolismo , Fructosa/efectos adversos , Estreptozocina/farmacología , Aprendizaje por Laberinto , Hipocampo/metabolismoRESUMEN
The root extract of Nauclea xanthoxylon (A.Chev.) Aubrév. displayed significant 50 % inhibition concentration (IC50 s) of 0.57 and 1.26â µg/mL against chloroquine resistant and sensitive Plasmodium falciparum (Pf) Dd2 and 3D7 strains, respectively. Bio-guided fractionation led to an ethyl acetate fraction with IC50 s of 2.68 and 1.85â µg/mL and subsequently, to the new quinovic acid saponin named xanthoxyloside (1) with IC50 s of 0.33 and 1.30â µM, respectively against the tested strains. Further compounds obtained from ethyl acetate and hexane fractions were the known clethric acid (2), ursolic acid (3), quafrinoic acid (4), quinovic acid (5), quinovic acid 3-O-ß-D-fucopyranoside (6), oleanolic acid (7), oleanolic acid 3-acetate (8), friedelin (9), ß-sitosterol (10a), stigmasterol (10b) and stigmasterol 3-O-ß-D-glucopyranoside (11). Their structures were characterised with the aid of comprehensive spectroscopic methods (1 and 2D NMR, Mass). Bio-assays were performed using nucleic acid gel stain (SYBR green I)-based fluorescence assay with chloroquine as reference. Extracts and compounds exhibited good selectivity indices (SIs) of >10. Significant antiplasmodial activities measured for the crude extract, the ethyl acetate fraction and xanthoxyloside (1) from that fraction can justify the use of the root of N. xanthoxylon in ethnomedicine to treat malaria.
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Antimaláricos , Rubiaceae , Saponinas , Antimaláricos/farmacología , Antimaláricos/química , Cloroquina/farmacología , Ácido Oleanólico , Extractos Vegetales/química , Plasmodium falciparum/metabolismo , Rubiaceae/química , Saponinas/química , Saponinas/farmacología , Ácido UrsólicoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Detarium microcarpum is used to treat typhoid fever, a major public health problem, by indigenous population in Africa. Though its preventive activities have been documented, the curative effect is still to be confirmed. AIM OF THE STUDY: This study aimed at evaluating the curative effects of the hydroethanolic extract of Detarium microcarpum root bark on Salmonella typhimurium-induced typhoid in rat and exploring the in-silico inhibition of some bacterial key enzymes. STUDY DESIGN: In vitro antioxydant, in vivo antisalmonella of the extract and in silico molecular docking assay on the isolated compounds were carried out to explore the anti-salmonella effects of Detarium microcarpum. MATERIAL AND METHODS: The in vitro antioxidant properties of the extract were evaluated using DPPH, ABTS and FRAP tests. The anti-salmonella activity of the extract was assessed through feacal sample from Salmonella typhimurium-infected rat cultured in Salmonella-Shigella agar (SS agar) medium. The affinity of isolated compounds (Rhinocerotinoic acid and Microcarposide) from the extract were performed on four key enzymes (Adenylosuccinate lyase, Acetyl coenzyme A synthetase, Thymidine phosphorylase and LuxS-Quorum sensor) using molecular docking simulation to elucidate the molecular level inhibition mechanism. RESULTS: Crude extract of D. microcarpum root bark showed variable activities on DPPH (RSa50: 6.09 ± 1.04 µg/mL), ABTS (RSa50: 24.46 ± 0.27), and FRAP (RSa50: 23.30 ± 0.23). The extract at all the doses exhibited significant healing effect of infected rats, with the complete clearance. The extract restored hematological, biochemical and histological parameters closed to the normal control. The molecular docking results indicates that rhinocerotinoic acid and microcarposide present more affinity to the LuxS-Quorum sensor and Acetyl coenzyme A synthetase protein as compared to the others. CONCLUSION: These results demonstrate potent anti-typhoid activities of the hydroethanolic of Detarium microcarpum root bark extract through antioxidant properties and high inhibitory affinity of its compounds on some bacterial key enzymes that justify its use as traditional medicine to typhoid fever.
Asunto(s)
Fabaceae , Fiebre Tifoidea , Ratas , Animales , Simulación del Acoplamiento Molecular , Extractos Vegetales/farmacología , Antioxidantes/farmacología , Fabaceae/química , Corteza de la Planta/química , Acetato CoA Ligasa/análisis , Agar/análisis , BacteriasRESUMEN
Phytoestrogens are used to ease postmenopausal symptoms, a property probably due to estrogenic and antioxidant effects. Pterocarpus soyauxii (P. soyauxii) is empirically used in Cameroon to treat among others primary and secondary amenorrhea. The aim of this study is to evaluate estrogenic and antioxidant activities of P. soyauxii heartwood aqueous extract in bilateral oophorectomized Wistar rats. Firstly, a characterization of the extract was carried out. For that, flavonoids, phenols, and tannins levels in P. soyauxii extract were evaluated by colorimetric assays and UHPLC-MS analysis was realized. In vitro antioxidant analysis of P. soyauxii was conducted using DPPH, ABTS, and FRAP assays. Secondly, 2 sets of pharmacologic tests were carried out. The results revealed that P. soyauxii aqueous extract contains, respectively, 229.42 ± 3.62 mg EAG/g, 63.42 ± 2.16 mg EQ/g, and 27.88 ± 0.23 mg ETA/g of polyphenols, flavonoids, and tannins. UHPLC-MS enabled identifying seven components including mono(2-ethylhexyl) phthalate, cembrene, 3',5'-dimethoxy-4-stilbenol, and linoleic acid. DPPH, ABTS, and FRAP assays revealed that P. soyauxii extract possessed a high antioxidant activity with IC50 value of 730.20 µg/mL, 892.90 µg/mL, and 765.75 mEAG/g of extract, respectively. In the uterotrophic assay, P. soyauxii extract induced significant increase of fresh uterine weight, uterine and vaginal epithelial size, and mammary glands differentiation compared to Ovx control. In the postmenopausal model, compared to the sham control, vagina and uterine dystrophies were observed in Ovx rats treated with distilled water. P. soyauxii aqueous extract expressed estrogenic-like effects on vagina and did not affect uterine epithelial height compared with vehicle groups. On the back of these vaginotrophic effects, the extract displayed antiatherogenic properties by reducing (p < 0.001) AI and LDL cholesterol level as compared to Ovx control group. The extract at 200 mg/kg significantly prevented the increase of MDA (p < 0.01) level and decreased nitrites (p < 0.001) and GSH (p < 0.01) levels compared to Ovx rats. These beneficial effects are related at least in part to the presence of compound such as mono(2-ethylhexyl) phthalate, 3',5'-dimethoxy-4-stilbenol, and linoleic acid. Overall, P. soyauxii aqueous extract exhibits estrogenic and antioxidant effects which can inhibit postmenopausal symptoms by providing vaginal stratification, improving lipid profile and insulin sensitivity, and reducing oxidative stress without side effects on the endometrium and mammary gland in 84-day Ovx rats.
RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Typhoid fever treatment remains a challenge in endemic countries. Detarium microcarpum is traditionally used to manage typhoid. AIM OF THE STUDY: The study aims to explore the efficacy of hydroethanolic extract of Detarium microcarpum root bark in rats infected with salmonella. MATERIAL AND METHODS: The phytochemical profile of the extract was obtained by UHPLC-MS analysis in an attempt of standardization. The in vitro antimicrobial activity was determined using broth dilution method. Salmonella infection was induced by oral administration of S. thyphimurium to immunosuppressed rats. Infected rats were then treated 2 h later with the extract (75, 150 and 300 mg/kg), distilled water (normal and salmonella control) and ciprofloxacin (8 mg/kg) for control. Body weight was monitored and stools were cultured to determine the number of colony-forming units. At the end of treatment, animals were sacrificed, blood and organs were collected for hematological, biochemical and histopathological analyses. RESULTS: Detarium microcarpum extract as well as the isolated compound (rhinocerotinoic acid) exhibited good antimicrobial activity in vitro with bacteriostatic effects. The plant extract significantly (p < 0.05) inhibited the bacterial development in infected animals with an effective dose (ED50) of 75 mg/kg. In addition, the extract prevented body weight loss, hematological, biochemical and histopathological damages in treated rats. CONCLUSION: Detarium microcarpum extract possesses antisalmonella properties justifying its traditional use for the typhoid fever management.