Unravelling the Influence of Chlorogenic Acid on the Antioxidant Phytochemistry of Avocado (Persea americana Mill.) Fruit Peel.

Oxidative stress is pivotal in the pathology of many diseases. This study investigated the antioxidant phytochemistry of avocado (Persea americana Mill.) peel. Different solvent extracts (dichloromethane, ethyl acetate, methanol, and water) of avocado peel were subjected to total phenol and flavonoid quantification, as well as in vitro radical scavenging and ferric reducing evaluation. The methanol extract was subjected to gradient column chromatographic fractionation. Fraction 8 (eluted with hexane:chloroform:methanol volume ratio of 3:6.5:0.5, respectively) was subjected to LC-MS analysis. It was assessed for cellular inhibition of lipid peroxidation and lipopolysaccharide (LPS)-induced ROS and NO production. The DPPH radical scavenging mechanism of chlorogenic acid was investigated using Density Functional Theory (DFT). The methanol extract and fraction 8 had the highest phenol content and radical scavenging activity. Chlorogenic acid (103.5 mg/mL) and 1-O-caffeoylquinic acid (102.3 mg/mL) were the most abundant phenolics in the fraction. Fraction 8 and chlorogenic acid dose-dependently inhibited in vitro (IC50 = 5.73 and 6.17 µg/mL) and cellular (IC50 = 15.9 and 9.34 µg/mL) FeSO4-induced lipid peroxidation, as well as LPS-induced ROS (IC50 = 39.6 and 28.2 µg/mL) and NO (IC50 = 63.5 and 107 µg/mL) production, while modulating antioxidant enzyme activity. The fraction and chlorogenic acid were not cytotoxic. DFT analysis suggest that an electron transfer, followed by proton transfer at carbons 3'OH and 4'OH positions may be the radical scavenging mechanism of chlorogenic acid. Considering this study is bioassay-guided, it is logical to conclude that chlorogenic acid strongly influences the antioxidant capacity of avocado fruit peel.

Genetic Signatures for Distinguishing Chemo-Sensitive from Chemo-Resistant Responders in Prostate Cancer Patients.

Prostate cancer remains a significant public health concern in sub-Saharan Africa, particularly impacting South Africa with high mortality rates. Despite many years of extensive research and significant financial expenditure, there has yet to be a definitive solution to prostate cancer. It is not just individuals who vary in their response to treatment, but even different nodules within the same tumor exhibit unique transcriptome patterns. These distinctions extend beyond mere differences in gene expression levels to encompass the control and networking of individual genes. Escalating chemotherapy resistance in prostate cancer patients has prompted increased research into its underlying mechanisms. The heterogeneous nature of transcriptomic organization among men makes the pursuit of universal biomarkers and one-size-fits-all treatments impractical. This study delves into the expression of drug resistance-associated genes, ABCB1 and CYP1B1, in cancer cells. Employing bioinformatics, we explored the molecular pathways and cascades linked to drug resistance following upregulation of these genes. Samples were obtained from archived prostate cancer patient specimens through pre-treatment biopsies of two categories: good vs. poor responders, with cDNAs synthesized from isolated RNAs subjected to qPCR analysis. The results revealed increased ABCB1 and CYP1B1 expression in tumor samples of the poor responders. Gene enrichment and network analysis associated ABCB1 with ABC transporters and LncRNA-mediated therapeutic resistance (WP3672), while CYP1B1 was linked to ovarian steroidogenesis, tryptophan metabolism, steroid hormone biosynthesis, benzo(a)pyrene metabolism, the sulindac metabolic pathway, and the estrogen receptor pathway, which are associated with drug resistance. Both ABCB1 and CYP1B1 correlated with microRNAs in cancer and the Nuclear Receptors Meta-Pathway. STRING analysis predicted protein-protein interactions of ABCB1 and CYP1B1 with Glutathione S-transferase Pi, Catechol O-methyltransferase, UDP-glucuronosyltransferase 1-6, Leucine-rich Transmembrane and O-methyltransferase (LRTOMT), and Epoxide hydrolase 1, with scores of 0.973, 0.971, 0.966, 0.966, and 0.966, respectively. Furthermore, molecular docking analysis of the chemotherapy drug, docetaxel, with CYP1B1 and ABCB1 revealed robust molecular interactions, with binding energies of -20.37 and -15.25 Kcal/mol, respectively. These findings underscore the susceptibility of cancer patients to drug resistance due to increased ABCB1 and CYP1B1 expression in tumor samples from patients in the poor-responders category that affects associated molecular pathways. The potent molecular interactions of ABCB1 and CYP1B1 with docetaxel further emphasize the potential basis for chemotherapy resistance.

Coconut (Cocos nucifera (L.)) Water Improves Glucose Uptake with Concomitant Modulation of Antioxidant and Purinergic Activities in Isolated Rat Psoas Muscles.

The present study investigated the effect of coconut water on glucose uptake and utilization, and metabolic activities linked to hyperglycemia in isolated rat psoas muscles. Coconut water was subjected to in vitro antioxidant and antidiabetic assays, which cover 2,2'-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity, ferric reducing antioxidant power (FRAP), and inhibition of α-glucosidase and α-amylase activities. Psoas muscles were isolated from male Sprague Dawley rats and incubated with coconut water in the presence of glucose. Control consisted of muscles incubated with glucose only, while normal control consisted of muscles not incubated in coconut water and/or glucose. The standard antidiabetic drug was metformin. Incubation with coconut water led to a significant increase in muscle glucose uptake, with concomitant exacerbation of glutathione level, and SOD and catalase activities, while suppressing malondialdehyde level, and ATPase and E-NTDase activities. Coconut water showed significant scavenging activity against DPPH, and significantly inhibited α-glucosidase and α-amylase activities. LC-MS analysis of coconut water revealed the presence of ellagic acid, butin, quercetin, protocatechuic acid, baicalin, and silibinin. Molecular docking analysis revealed potent molecular interactions between the LC-MS-identified compounds, and AKT-2 serine and PI-3 kinase. These results indicate the potential of coconut water to enhance glucose uptake, while concomitantly improving antioxidative and purinergic activities. They also indicate the potential of coconut water to suppress postprandial hyperglycemia. These activities may be attributed to the synergistic effects of the LC-MS-identified compounds.

Phytochemical Properties of Croton gratissimus Burch (Lavender Croton) Herbal Tea and Its Protective Effect against Iron-Induced Oxidative Hepatic Injury.

Oxidative stress plays a vital role in the pathogenesis and progression of various liver diseases. Traditional medicinal herbs have been used worldwide for the treatment of chronic liver diseases due to their high phytochemical constituents. The present study investigated the phytochemical properties of Croton gratissimus (lavender croton) leaf herbal tea and its hepatoprotective effect on oxidative injury in Chang liver cells, using an in vitro and in silico approach. C. gratissimus herbal infusion was screened for total phenolic and total flavonoid contents as well as in vitro antioxidant capacity using ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picryl-hydrazyl (DPPH) methods. Oxidative hepatic injury was induced by incubating 0.007 M FeSO4 with Chang liver cells which has been initially incubated with or without different concentrations (15-240 µg/mL) of C. gratissimus infusion or the standard antioxidants (Gallic acid and ascorbic acid). C. gratissimus displayed significantly high scavenging activity and ferric reducing capacity following DPPH and FRAP assays, respectively. It had no cytotoxic effect on Chang liver cells. C. gratissimus also significantly elevated the level of hepatic reduced glutathione (GSH), superoxide dismutase (SOD), and catalase activities as well as suppressed the malondialdehyde (MDA) level in oxidative hepatic injury. Liquid Chromatography-Mass Spectrometry (LC-MS) analysis of the herbal tea revealed the presence of 8-prenylnaringenin, flavonol 3-O-D-galactoside, caffeine, spirasine I, hypericin, pheophorbide-a, and 4-methylumbelliferone glucuronide. In silico oral toxicity prediction of the identified phytochemicals revealed no potential hepatotoxicity. Molecular docking revealed potent molecular interactions of the phytochemicals with SOD and catalase. The results suggest the hepatoprotective and antioxidative potentials of C. gratissimus herbal tea against oxidative hepatic injury.

Lippia javanica (Burm. F.) Herbal Tea: Modulation of Hepatoprotective Effects in Chang Liver Cells via Mitigation of Redox Imbalance and Modulation of Perturbed Metabolic Activities.

Introduction: Hepatic oxidative injury is one of the pathological mechanisms that significantly contributes to the development of several liver diseases. In the present study, the hepatoprotective effect of Lippia javanica herbal tea was investigated in Fe2+- mediated hepatic oxidative injury. Methods: Using an in vitro experimental approach, hepatic oxidative injury was induced by co-incubating 7 mM FeSO4 with Chang liver cells that have been pre-incubated with or without different concentrations (15-240 µg/mL) of L. javanica infusion. Gallic acid and ascorbic acid served as the standard antioxidants. Results: The infusion displayed a reducing antioxidant activity in ferric-reducing antioxidant power (FRAP) assay and a potent scavenging activity on 2,2-diphenyl-2- picrylhydrazyl (DPPH) radical. Pretreatment with L. javanica infusion significantly elevated the levels of reduced glutathione and non-protein thiol, and the activities of superoxide dismutase (SOD) and catalase, with concomitant decrease in hepatic malondialdehyde levels, acetylcholinesterase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glycogen phosphorylase and lipase activities. The infusion showed the presence of phytoconstituents such as phenolic compounds, tannins, phenolic glycosides and terpenoids when subjected to liquid chromatography-mass spectrometry analysis. Molecular docking revealed a strong binding affinity of dihydroroseoside and obacunone with both SOD and catalase compared to other phytoconstituents. Conclusion: These results portray a potent antioxidant and hepatoprotective effect of L. javanica, which may support the local usage of the herbal tea as a prospective therapeutic agent for oxidative stress-related liver diseases.

Cannabis sativa L. modulates altered metabolic pathways involved in key metabolisms in human breast cancer (MCF-7) cells: A metabolomics study.

The present study investigated the ability of Cannabis sativa leaves infusion (CSI) to modulate major metabolisms implicated in cancer cells survival, as well as to induce cell death in human breast cancer (MCF-7) cells. MCF-7 cell lines were treated with CSI for 48 h, doxorubicin served as the standard anticancer drug, while untreated MCF-7 cells served as the control. CSI caused 21.2% inhibition of cell growth at the highest dose. Liquid chromatography-mass spectroscopy (LC-MS) profiling of the control cells revealed the presence of carbohydrate, vitamins, oxidative, lipids, nucleotides, and amino acids metabolites. Treatment with CSI caused a 91% depletion of these metabolites, while concomitantly generating selenomethionine, l-cystine, deoxyadenosine triphosphate, cyclic AMP, selenocystathionine, inosine triphosphate, adenosine phosphosulfate, 5'-methylthioadenosine, uric acid, malonic semialdehyde, 2-methylguanosine, ganglioside GD2 and malonic acid. Metabolomics analysis via pathway enrichment of the metabolites revealed the activation of key metabolic pathways relevant to glucose, lipid, amino acid, vitamin, and nucleotide metabolisms. CSI caused a total inactivation of glucose, vitamin, and nucleotide metabolisms, while inactivating key lipid and amino acid metabolic pathways linked to cancer cell survival. Flow cytometry analysis revealed an induction of apoptosis and necrosis in MCF-7 cells treated with CSI. High-performance liquid chromatography (HPLC) analysis of CSI revealed the presence of cannabidiol, rutin, cinnamic acid, and ferulic. These results portray the antiproliferative potentials of CSI as an alternative therapy for the treatment and management of breast cancer as depicted by its modulation of glucose, lipid, amino acid, vitamin, and nucleotide metabolisms, while concomitantly inducing cell death in MCF-7 cells.

Butanol fraction of Alstonia boonei De Wild. leaves ameliorate oxidative stress and modulate key hypoglycaemic processes in diabetic rats.

OBJECTIVE: The effect of Alstonia boonei fractions on glucose homeostasis was investigated via in vitro enzyme inhibition activity, ex vivo glucose uptake assay, and in vivo methods in diabetic rats. METHODOLOGY: A. boonei fractions were subjected to in vitro α-glucosidase inhibitory assay and then ex vivo glucose uptake activity. The butanol fraction of the leaves (ABBF) was picked for the in vivo assay since it showed more activity in the initial tests conducted. ABBF was administrated via oral dosing to six-weeks old fructose-fed STZ-induced type 2 diabetic rats over a 5-week experimental period. RESULTS: ABBF treatment at a low dose of 150 mg/kg bw, significantly (p < .05) reduced blood glucose level, enhanced oral glucose tolerance ability, restored insulin secretion and hepatic glycogen synthesis as well as promoted islet regeneration than the high dose (300 mg/kg bw). CONCLUSION: These results suggest that ABBF could be exploited as a therapeutic potential for treating T2D.

Kolaviron modulates dysregulated metabolism in oxidative pancreatic injury and inhibits intestinal glucose absorption with concomitant stimulation of muscle glucose uptake.

This present study investigated the antioxidative and antidiabetic properties of kolaviron by analysing its inhibitory effect on key metabolic activities linked to T2D, in vitro and ex vivo. Kolaviron significantly inhibited α-glucosidase and α-amylase activities, and intestinal glucose absorption dose-dependently, while promoting muscle glucose uptake. Induction of oxidative pancreatic injury significantly depleted glutathione level, superoxide dismutase, catalase, and ATPase activities, while elevating malondialdehyde and nitric oxide levels, acetylcholinesterase and chymotrypsin activities. These levels and activities were significantly reversed in tissues treated with kolaviron. Kolaviron depleted oxidative-induced metabolites, with concomitant restoration of oxidative-depleted metabolites. It also inactivated oxidative-induced ascorbate and aldarate metabolism, pentose and glucuronate interconversions, fructose and mannose metabolism, amino sugar and nucleotide sugar metabolism, and arginine and proline metabolism, while reactivating selenocompound metabolism. These results depict the antidiabetic properties of kolaviron as indicated by its ability to attenuate oxidative-induced enzyme activities and dysregulated metabolisms, and modulated the enzyme activities linked to hyperglycaemia.

Ferulic acid mitigates diabetic cardiomyopathy via modulation of metabolic abnormalities in cardiac tissues of diabetic rats.

Cardiovascular abnormalities have been reported as a major contributor of diabetic mortality. The protective effect of ferulic acid on diabetic cardiomyopathy in fructose-streptozotocin induced type 2 diabetes (T2D) rat model was elucidated in this study. Type 2 diabetic rats were treated by oral administration of low (150 mg/kg b.w) and high (300 mg/kg b.w) doses of ferulic acid. Metformin was used as the antidiabetic drug. Rats were humanely euthanized after 5 weeks of treatment, and their blood and hearts were collected. Induction of T2D depleted the levels of reduced glutathione, glycogen, and HDL-cholesterol and the activities of superoxide dismutase, catalase, ENTPDase, and 5'nucleotidase. It simultaneously triggered increase in the levels of malondialdehyde, total cholesterol, triglyceride, LDL-cholesterol, creatinine kinase-MB as well as activities of acetylcholinesterase, angiotensin converting enzyme (ACE), ATPase, glucose-6-phopsphatase, fructose-1,6-bisphophatase, glycogen phosphorylase, and lipase. T2D induction further revealed an obvious degeneration of cardiac muscle morphology. However, treatment with ferulic acid markedly reversed the levels and activities of these biomarkers with concomitant improvement in myocardium structural morphology, which had favorable comparison with the standard drug, metformin. Additionally, T2D induction led to the depletion of 40%, 75%, and 33% of fatty acids, fatty esters, and steroids, respectively, with concomitant generation of eicosenoic acid, gamolenic acid, and vitamin E. Ferulic acid treatment restored eicosanoic acid, 2-hydroxyethyl ester, with concomitant generation of 6-octadecenoic acid, (Z)-, cis-11-eicosenoic acid, tridecanedioic acid, octadecanoic acid, 2-hydroxyethyl ester, ethyl 3-hydroxytridecanoate, dipalmitin, cholesterol isocaproate, cholest-5-ene, 3-(1-oxobuthoxy)-, cholesta-3,5-diene. These results suggest the cardioprotective potential of ferulic acid against diabetic cardiomyopathy.

Ferulic acid improves glucose homeostasis by modulation of key diabetogenic activities and restoration of pancreatic architecture in diabetic rats.

There are increasing concerns on the rising cases of diabetes mellitus with type 2 diabetes (T2D) being of major interest as well as the cost of its treatment. Plant phenolic compounds are natural and potent antioxidants that have been widely reported for their antidiabetic activities properties, one of which is ferulic acid. The effect of ferulic acid (FA) on major diabetogenic activities and pancreatic architecture linked to T2D was investigated in T2D rats. T2D was induced in male Sprague-Dawley rats using the fructose-streptozotocin model. Diabetic rats were treated with FA at 150 or 300 mg/kg bodyweight (bw). Normal control consisted of rats administered with food and water, while diabetic control consisted of untreated diabetic rats. Metformin was used as the standard drug. The rats were humanely sacrificed after 5 weeks of treatment. Their blood, liver, and pancreas were collected for analysis. Total glycogen content and carbohydrate metabolic enzymes activities were analyzed in the liver, while the pancreas and serum from blood were analyzed for oxidative stress biomarkers, purinergic and cholinergic enzyme activities, and amylase and lipase activities. The pancreatic tissue was further subjected to microscopic and histological examinations. FA caused a significant (p < 0.05) decrease in blood glucose level, with concomitant increase in serum insulin level. Treatment with FA also led to elevated levels of GSH, HDL-c, SOD, and catalase activities, while concomitantly suppressing malondialdehyde, cholesterol, triglyceride, LDL-c, NO, ALT, AST, creatinine, urea, and uric acid levels, acetylcholinesterase, ATPase, ENTPDase, 5'-nucleotidase, lipase, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-biphosphatase activities. Histology analysis revealed an intact pancreatic morphology in FA-treated diabetic rats. While transmission electron microscopy (TEM) analysis revealed an intact pancreatic ultrastructure and increased number of insulin granules in ß-cells. Taken together, these results portray that the antidiabetic potentials of ferulic acid involves modulation of major diabetogenic activities and maintenance of the pancreatic ultrastructure architecture.

Senna petersiana (Bolle) leaf extract modulates glycemic homeostasis and improves dysregulated enzyme activities in fructose-fed streptozotocin-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Senna petersiana (Bolle) is a native South African medicinal shrub combined locally with other plant products to manage diabetes or used as a single therapy for several other ailing conditions. AIM OF THE STUDY: This study evaluated the antidiabetic and antilipidemic effects of S. petersiana leaf ethanol extract and its modulatory effects on dysregulated enzyme activities in fructose-fed streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Six groups of 6-weeks old male Sprague Dawley rats were used in this study. Diabetes was induced in four of the groups by injecting (i.p.) 40 mg/kg of streptozotocin after a two-weeks feeding of 10% fructose via drinking water, while animals in the two normal groups were given similar volume of vehicle buffer and normal drinking water, respectively. After the confirmation of diabetes, treatment with 150 and 300 mg/kg body weight of the ethanolic leaf extract of S. petersiana proceeded for a period of 6 weeks. RESULTS: Oral administration of S. petersiana leaf extract significantly lowered blood glucose, food and liquid intake, glycosylhaemoglobin in blood, liver and cardiac biomarkers, and lipid profile in serum and atherogenic index (AIP) in both the low and high-dose treated animal groups. This was accompanied by a simultaneous increase in Homeostatic Model Assessment-beta (HOMA-ß) score, serum high-density lipoproteins cholesterol (HDL-c), and insulin levels. It also improved pancreatic and serum-reduced glutathione (GSH) levels, catalase, and superoxide dismutase (SOD) enzymes activities with a simultaneous reduction in malondialdehyde (MDA) and nitric oxide (NO) concentrations. Moreover, the extract modulated dysregulated α-amylase, lipase, cholinesterase, and 5' nucleotidase enzyme activities in pancreatic tissue as well as glycogen metabolism in the liver. Analysis of the phytochemicals in the S. petersiana extract showed the presence of phytol, 4a,7,7,10a-tetramethyldodecahydrobenzo[f]-chromen-3-ol, phytol acetate, solasodine glucoside, cassine, veratramine and solasodine acetate. Amongst these compounds, solasodine glucoside had the best binding energy (ΔG) with the selected diabetes-linked enzymes via molecular docking simulation. CONCLUSION: Data from this study demonstrate the antidiabetic effects of S. petersiana leaf extract via the modulation of the dysregulated indices involved in type 2 diabetes and its associated complications. Although it has been shown safe in animals, further toxicological studies are required to ensure its safety for diabetes management in humans.

Hibiscus sabdariffa L. polyphenolic-rich extract promotes muscle glucose uptake and inhibits intestinal glucose absorption with concomitant amelioration of Fe2+ -induced hepatic oxidative injury.

In this current study, the antidiabetic effectiveness of Hibiscus sabdariffa and its protective function against Fe2+ -induced oxidative hepatic injury were elucidated using in vitro, in silico, and ex vivo studies. The oxidative damage was induced in hepatic tissue by incubation with 0.1 mMolar ferrous sulfate (FeSO4) and then treated with different concentrations of crude extracts (ethyl acetate, ethanol, and aqueous) of H. sabdariffa flowers for 30 min at 37°C. When compared to ethyl acetate and aqueous extracts, the ethanolic extract displayed the most potent scavenging activity in ferric-reducing antioxidant power (FRAP), 1,1-diphenyl-2-picrylhydrazyl (DPPH), and nitric oxide (NO) assays, with IC50 values of 2.8 µl/ml, 3.3 µl/ml, and 9.2 µl/ml, respectively. The extracts significantly suppressed α-glucosidase and α-amylase activities (p < .05), with the ethanolic extract demonstrating the highest activity. H. sabdariffa significantly (p < .05) raised reduced glutathione (GSH) levels while simultaneously decreasing malondihaldehyde (MDA) and NO levels and increasing superoxide dismutase (SOD) and catalase activity in Fe2+ induced oxidative hepatic injury. The extract of the plant inhibited intestinal glucose absorption and increased muscular glucose uptake. The extract revealed the presence of several phenolic compounds when submitted to gas chromatography-mass Spectroscopy (GC-MS) screening, which was docked with α-glucosidase and α- amylase. The molecular docking displayed the compound 4-(3,5-Di-tert-butyl-4-hydroxyphenyl)butyl acrylate strongly interacted with α-glucosidase and α-amylase and had the lowest free binding energy compared to other compounds and acarbose. These results suggest that H. sabdariffa has promising antioxidant and antidiabetic activity. PRACTICAL APPLICATIONS: In recent years, there has been increased concern about the side effects of synthetic anti-diabetic drugs, as well as their expensive cost, especially in impoverished nations. This has instigated a radical shift towards the use of traditional plants, which are rich in phytochemicals many years ago. Among these plants, H. sabdariffa has been used to treat diabetes in traditional medicine. In this present study, H. sabdariffa extracts demonstrated the ability to inhibit carbohydrate digesting enzymes, facilitate muscle glucose uptake and attenuate oxidative stress in oxidative hepatic injury. Hence, demonstrating H. sabdariffa's potential to protect against oxidative damage and the complications associated with diabetes. Consumption of Hibiscus tea or juice may be a potential source for developing an anti-diabetic drug.

Underutilized legumes, Cajanus cajan and Glycine max may bring about antisickling effect in sickle cell disease by modulation of redox homeostasis in sickled erythrocytes and alteration of its functional chemistry.

The antisickling and anti-oxidative effect of the Cajanus cajan, Glycine max, and their blends were investigated in sickled erythrocytes. The powdered samples were analyzed for their nutritional and anti-nutritional constituents. Their aqueous extracts were analyzed for in vitro antioxidant activities. The extracts were incubated with sickled erythrocytes at 37°C for 6 hours and the antisickling effect examined via microscopic analysis. The blend was the most active and its incubated cells were subjected to anti-oxidative analysis which covers for GSH, SOD, catalase, and lipid peroxidation (LPO). Chemical functional group of the treated cells was analyzed with FTIR spectroscopy. The in silico binding of the predominant amino acid to hemoglobin was also investigated. An increased concentration of leucine was observed in the blend compared to that of C. cajan and G. max, respectively. Vitamins C, B6, and B9 were the only vitamins observed in the blend. Phytate and oxalate were present in all samples. All extracts displayed significant (p < .05) scavenging activities. Treatment with the blend exacerbated SOD and catalase activities as well as the GSH level, while suppressing LPO. FTIR analysis of the treated cells showed the presence of hydrophobic functional groups. Leucine was the predominant amino acid, and it showed a potent molecular interaction with HIS-87 residue of the alpha chain of 1HCO. C. cajan and G. max blend inhibited sickling activities of sickle erythrocytes, while concomitantly exacerbating their endogenous antioxidant enzymes activity and modification of the functional chemistry. PRACTICAL APPLICATIONS: Cajanus cajan and Glycine max are among the common underutilized legumes in Nigeria. Aside their nutritional properties, these legumes have been used from time immemorial for the treatment and management of various ailments. Sickle cell anemia is a class of hemoglobinopathy common in Sub-Saharan Africa. There have been concerns about its treatment owing to the increasing scourge of the disease coupled to the financial burden of its management. This study reports the ability of the potentials of the legumes to prevent sickling activities of sickled erythrocytes and the possible biochemical mechanism involved.

In vitro study on efficacy of PHELA, an African traditional drug against SARS-CoV-2.

In 2019, coronavirus has made the third apparition in the form of SARS-CoV-2, a novel strain of coronavirus that is extremely pathogenic and it uses the same receptor as SARS-CoV, the angiotensin-converting enzyme 2 (ACE2). However, more than 182 vaccine candidates have been announced; and 12 vaccines have been approved for use, although, even vaccinated individuals are still vulnerable to infection. In this study, we investigated PHELA, recognized as an herbal combination of four exotic African medicinal plants namely; Clerodendrum glabrum E. Mey. Lamiaceae, Gladiolus dalenii van Geel, Rotheca myricoides (Hochst.) Steane & Mabb, and Senna occidentalis (L.) Link; as a candidate therapy for COVID-19. In vitro testing found that PHELA inhibited > 90% of SARS-CoV-2 and SARS-CoV infection at concentration levels of 0.005 mg/ml to 0.03 mg/ml and close to 100% of MERS-CoV infection at 0.1 mg/ml to 0.6 mg/ml. The in vitro average IC50 of PHELA on SARS-COV-2, SARS-CoV and MERS-COV were ~ 0.01 mg/ml. Secondly in silico docking studies of compounds identified in PHELA showed very strong binding energy interactions with the SARS-COV-2 proteins. Compound 5 showed the highest affinity for SARS-COV-2 protein compared to other compounds with the binding energy of - 6.8 kcal mol-1. Our data showed that PHELA has potential and could be developed as a COVID-19 therapeutic.

Caffeic acid regulates glucose homeostasis and inhibits purinergic and cholinergic activities while abating oxidative stress and dyslipidaemia in fructose-streptozotocin-induced diabetic rats.

OBJECTIVES: The antidiabetic potential of caffeic acid in fructose/streptozotocin-induced type 2 diabetic rats was examined in this study. METHODS: Male Sprague-Dawley rats were supplied with 10% fructose solution for 14 days followed by an intraperitoneal injection of 40 mg/kg bw streptozotocin to induce type 2 diabetes (T2D). Rats were treated with both low (150 mg/kg bw) and high (300 mg/kg bw) doses of caffeic acid for 5 weeks, while the positive control group was treated with metformin (200 mg/kg bw). KEY FINDINGS: Treatment with caffeic acid significantly decreased blood glucose levels and elevated serum insulin levels while improving glucose tolerance, pancreatic ß-cell function and morphology. It also led to a significant reduction of serum cholesterol, triglyceride, LDL-cholesterol, ALT, AST, creatinine, urea and uric acid levels, while increasing HDL cholesterol levels. Caffeic acid significantly (P < 0.05) elevated hepatic glycogen level, serum and pancreatic glutathione level, superoxide dismutase and catalase activities with a concomitant decrease in malondialdehyde level, α-amylase, lipase, adenosine triphosphatase (ATPase), ectonucleoside triphosphate diphosphohydrolase (ENTPDase), 5'-nucleotidase (5'-NTD) and acetylcholinesterase activities. CONCLUSION: The results suggest caffeic acid as a potent natural product with therapeutic effects against T2D. Further molecular and clinical studies are, however, required to ascertain these findings.

Cannabis sativa L. protects against oxidative injury in kidney (vero) cells by mitigating perturbed metabolic activities linked to chronic kidney diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Cannabis sativa L. is among numerous medicinal plants widely used in traditional medicine in treating various ailments including kidney diseases. AIMS: The protective effect of C. sativa on oxidative stress, cholinergic and purinergic dysfunctions, and dysregulated glucogenic activities were investigated in oxidative injured kidney (Vero) cell lines. METHODS: Fixed Vero cells were treated with sequential extracts (hexane, dichloromethane [DCM] and ethanol) of C. sativa leaves for 48 h before subjecting to MTT assay. Vero cells were further incubated with FeSO4 for 30 min, following pretreatment with C. sativa extracts for 25 min. Normal control consisted of Vero cells not treated with the extracts and/or FeSO4, while untreated (negative) control consisted of cells treated with only FeSO4. RESULTS: MTT assay revealed the extracts were slightly cytotoxic at the highest concentrations (250 µg/mL). There was a significant depletion in glutathione level and catalase activity on induction of oxidative stress, with significant elevation in malondialdehyde level, acetylcholinesterase, ATPase, ENTPDase, fructose-1,6-biphosphatase, glucose 6-phosphatase and glycogen phosphorylase activities. These activities and levels were significantly reversed following pretreatment with C. sativa extracts. CONCLUSION: These results portray the protective potentials of C. sativa against iron-mediated oxidative renal injury as depicted by the ability of its extracts to mitigate redox imbalance and suppress acetylcholinestererase activity, while concomitantly modulating purinergic and glucogenic enzymes activities in Vero cells.

Harpephyllum caffrum fruit (wild plum) facilitates glucose uptake and modulates metabolic activities linked to neurodegeneration in isolated rat brain: An in vitro and in silico approach.

Alteration in brain glucose metabolism due to glucose uptake reduction has been described in the onset of certain neurodegenerative disorders. This study determined Harpephyllum caffrum fruit's potential ability to improve glucose uptake and its modulatory effects on intrinsic antioxidant, glucogenic, cholinergic, and nucleotide-hydrolyzing enzyme activities in isolated rat brain. Consequently, the bioactive compounds of the fruits were identified with LC-MS. The fruit significantly improved brain glucose uptake following coincubation with glucose and brain tissue. The fruit extract also elevated GSH level, SOD, catalase, glycogen phosphorylase, and ENTPDase activities while simultaneously suppressing NO and malonaldehyde levels and fructose-1,6-bisphosphatase, ATPase, acetylcholinesterase and butyrylcholinesterase activities. LC-MS analysis revealed S-methylcysteine sulfoxide, dihydroquercetin, 3,4-dimethyl-2,5-bis(3,4,5-trimethoxyphenyl) tetrahydrofuran (MTHF), nobiletin, puerarin, quercetin 3-rutinoside, 8-D-glucosyl-4',5,7-trihydroxyflavone, asperulosidic acid, 1,2,4,6-tetragalloylglucose, and phellamurin. This study suggests the neuroprotective effects of H. caffrum fruit due to its ability to enhance glucose uptake, attenuate glucose-induced oxidative stress while modulating glucogenic, cholinergic, and nucleotide-hydrolyzing enzyme activities in normal brain tissues. PRACTICAL APPLICATIONS: Available scientific evidence describes oxidative stress as one of the physiological processes contributing to aging-associated neurodegeneration in humans. In this regard, commonly consumed natural products from plants have attracted much interest due to their ability to mitigate redox imbalance-related pathologies that affect various organs in the body such as the brain. Harpephyllum caffrum or bush mango is an evergreen plant native to the South African vegetation. The fruit from the plant is consumed locally as food or specifically for improving the nutritional quality of meals as deserts or condiments. While previous findings described the high antioxidant properties of the fruits, this study reported possible mechanisms via which the plant may exhibit ameliorative effects against oxidative stress-related neurological disorders in the brain. Hence, findings from the current work present another justification for the significance of fruits as a safer nutraceutical alternative for therapy in neurological disease management.

Cannabidiol improves glucose utilization and modulates glucose-induced dysmetabolic activities in isolated rats' peripheral adipose tissues.

Reduced glucose uptake and utilization, with concomitant lipolysis in adipose tissues has been linked to the pathogenesis of obesity and its complications. The present study investigated the effect of cannabinoid-stimulated glucose uptake on redox imbalance, glucose and lipid metabolisms, as well as cholinergic and purinergic dysfunctions in isolated rats' adipose tissues. Freshly Isolated rats' adipose tissues were incubated with glucose and different concentrations of cannabidiol for 2 h at 37 °C. The negative control consisted of incubation without cannabidiol, while normal control consisted of incubations without glucose and/or cannabidiol and Metformin served as the standard drug. Cannabidiol caused an increase in adipose-glucose uptake, with concomitant elevation of glutathione, triglyceride level, superoxide dismutase, catalase and 5'nucleoidase activities. It also caused suppression in malondialdehyde and cholesterol levels, acetylcholinesterase, ENTPDase, fructose-1,6-biphosphatase, glucose 6-phosphatase, glycogen phosphorylase, and lipase activities. In silico studies revealed a strong molecular interaction of cannabidiol with adipose triglyceride lipase, hormone-sensitive lipase, and monoglyceride lipase. These results indicate that cannabidiol-enhanced glucose uptake in adipose tissues is associated with enhanced antioxidative activities, concomitant modulation of cholinergic and purinergic dysfunctions, and improved glucose - lipid homeostasis.

Kolaviron Ameliorates 7, 12-Dimethylbenzanthracene - Induced Mammary Damage.

BACKGROUND: Kolaviron (KV) is a flavonoid-rich portion obtained from Garcinia kola seeds with a number of reported pharmacological effects. However, its ameliorative effects on 7,12-Dimethylbenzanthracene (DMBA)-induced mammary damage has not been fully investigated, despite the reported use of the seeds in the treatment of inflammatory related disorders. OBJECTIVE: To evaluate the ameliorative effects of KV on DMBA-induced mammary damage in female Wistar rats. METHODS: Forty-nine (49) female Wistar rats were randomly assigned into seven groups of seven rats each. DMBA was administered orally to rats in five of the groups as a single dose of 80 mg/kg body wt while the remaining two groups received the vehicle. The rats were palpated weekly for 3 months to monitor tumor formation. After 3 months of DMBA administration, 1 ml of blood was collected to assay for estrogen receptor- α (ER-α) level. Thereafter, the vehicle (dimethyl sulfoxide) was daily administered to the negative control and positive control groups for the 14 days duration of the experiment while three groups were each given a daily oral dose of 50, 100, and 200 mg/kg body wt of KV for the duration of the experiment. The last DMBA-induced group received 10 mg/kg body wt of the standard drug tamoxifen twice a week, and the remaining DMBA-free group received 200 mg/kg body wt KV. Subsequently, the animals were humanely sacrificed, and ER-α, sialic acids, sialidase, sialyltransferase levels were assayed in blood and mammary tissues followed by histopathological examinations. RESULTS: Significantly higher levels of estrogen receptor-α (ER-α), formation of lobular neoplastic cells, epithelial hyperplasia, lymphocyte infiltration, and increased sialylation were detected in DMBA-induced rats. Treatment with KV at 50, 100, and 200 mg/kg body weight resulted in a significant (p<0.05) decrease in ER-α level, free serum sialic acid (21.1%), the total sialic acid level of the mammary tissue (21.57%), sialyltransferase activity (30.83%) as well as mRNA level of the sialyltransferase gene (ST3Gal1) were observed after KV interventions. CONCLUSION: The findings suggest that KV could be further explored in targeting DMBA-induced mammary damage implicated in mammary carcinogenesis.