Phytochemical evaluation of Ziziphus mucronata and Xysmalobium undulutum towards the discovery and development of anti-malarial drugs.

BACKGROUND: The development of resistance by Plasmodium falciparum is a burdening hazard that continues to undermine the strides made to alleviate malaria. As such, there is an increasing need to find new alternative strategies. This study evaluated and validated 2 medicinal plants used in traditional medicine to treat malaria. METHODS: Inspired by their ethnobotanical reputation of being effective against malaria, Ziziphus mucronata and Xysmalobium undulutum were collected and sequentially extracted using hexane (HEX), ethyl acetate (ETA), Dichloromethane (DCM) and methanol (MTL). The resulting crude extracts were screened for their anti-malarial and cytotoxic potential using the parasite lactate dehydrogenase (pLDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, respectively. This was followed by isolating the active compounds from the DCM extract of Z. mucronata using silica gel chromatography and structural elucidation using spectroscopic techniques (NMR: 1H, 12C, and DEPT). The active compounds were then targeted against P. falciparum heat shock protein 70-1 (PfHsp70-1) using Autodock Vina, followed by in vitro validation assays using ultraviolet-visible (UV-VIS) spectroscopy and the malate dehydrogenase (MDH) chaperone activity assay. RESULTS: The extracts except those of methanol displayed anti-malarial potential with varying IC50 values, Z. mucronata HEX (11.69 ± 3.84 µg/mL), ETA (7.25 ± 1.41 µg/mL), DCM (5.49 ± 0.03 µg/mL), and X. undulutum HEX (4.9 ± 0.037 µg/mL), ETA (17.46 ± 0.024 µg/mL) and DCM (19.27 ± 0.492 µg/mL). The extracts exhibited minimal cytotoxicity except for the ETA and DCM of Z. mucronata with CC50 values of 10.96 and 10.01 µg/mL, respectively. Isolation and structural characterization of the active compounds from the DCM extracts revealed that betulinic acid (19.95 ± 1.53 µg/mL) and lupeol (7.56 ± 2.03 µg/mL) were responsible for the anti-malarial activity and had no considerable cytotoxicity (CC50 > µg/mL). Molecular docking suggested strong binding between PfHsp70-1, betulinic acid (- 6.8 kcal/mol), and lupeol (- 6.9 kcal/mol). Meanwhile, the in vitro validation assays revealed the disruption of the protein structural elements and chaperone function. CONCLUSION: This study proves that X undulutum and Z. mucronata have anti-malarial potential and that betulinic acid and lupeol are responsible for the activity seen on Z. mucronata. They also make a case for guided purification of new phytochemicals in the other extracts and support the notion of considering medicinal plants to discover new anti-malarials.

Morphed aflaxotin concentration produced by Aspergillus flavus strain VKMN22 on maize grains inoculated on agar culture.

This study identified and monitored the levels of aflatoxins (B1 and B2) produced by Aspergillus flavus isolate VKMN22 (OP355447) in maize samples sourced from a local shop in Johannesburg, South Africa. Maize samples underwent controlled incubation after initial rinsing, and isolates were identified through morphological and molecular methods. In another experiment, autoclaved maize grains were intentionally re-inoculated with the identified fungal isolate using spore suspension (106 spore/mL), after which 1 g of the contaminated maize sample was inoculated on PDA media and cultured for seven days. The aflatoxin concentrations in the A. flavus contaminated maize inoculated on culture media was monitored over seven weeks and then measured using liquid chromatography-mass spectroscopy (LC-MS). Results confirmed the successful isolation of A. flavus strain VKMN22 with accession number OP355447, which consistently produced higher levels of AFB1 compared to AFB2. AF concentrations increased from week one to five, then declined in week six and seven. AFB1 levels ranged from 594.3 to 9295.33 µg/kg (week 1-5) and then reduced from 5719.67 to 2005 µg/kg in week six and seven), while AFB2 levels ranged from 4.92 to 901.67 µg/kg (weeks 1-5) and then degraded to 184 µg/kg in week six then 55.33 µg/kg (weeks 6-7). Levene's tests confirmed significantly higher mean concentrations of AFB1 compared to AFB2 (p ≤ 0.005). The study emphasizes the importance of consistent biomonitoring for a dynamic understanding of AF contamination, informing accurate prevention and control strategies in agricultural commodities thereby safeguarding food safety.

Experimental models of lipid overload and their relevance in understanding skeletal muscle insulin resistance and pathological changes in mitochondrial oxidative capacity.

It remains essential to decipher some of the pathological mechanisms that link obesity with deteriorating human health. Insulin resistance, due to enhanced free fatty acid substrate delivery, results in disrupted glucose homeostasis and altered mitochondrial oxidative capacity, which is a characteristic feature of an obese state. In fact, as a major site for regulating glucose homeostasis and energy production in response to insulin, the skeletal muscle has become an interesting target tissue to understand the impact of lipid overload on the development of insulin resistance and impaired mitochondrial respiratory function. In addition to systematically retrieving the discussed data, the current review brings an essential perspective in understanding the relevance of experimental models of lipid overload such as high fat diets in understanding the pathological link between insulin resistance and pathological changes in mitochondrial oxidative capacity. Importantly, inclusion of evidence from transgenic model highlights some of the unique molecular targets that are implicated in the development of insulin resistance and inefficient mitochondrial respiration processes within an obese state. Importantly, saturation with lipid products such as ceramides and diacylglycerols, especially within the skeletal muscle, appears to be instrumental in paving the path leading to worsening of metabolic complications. These metabolic consequences mostly interfere with the efficiency of the mitochondrial electron transport chain, leading to overproduction of toxic reactive oxygen species. Therefore, therapeutic agents that reverse the effects of lipid overload by improving insulin sensitivity and mitochondrial oxidative capacity are crucial for the management or even treatment of metabolic diseases.

Rooibos Flavonoids, Aspalathin, Isoorientin, and Orientin Ameliorate Antimycin A-Induced Mitochondrial Dysfunction by Improving Mitochondrial Bioenergetics in Cultured Skeletal Muscle Cells.

The current study investigated the physiological effects of flavonoids found in daily consumed rooibos tea, aspalathin, isoorientin, and orientin on improving processes involved in mitochondrial function in C2C12 myotubes. To achieve this, C2C12 myotubes were exposed to a mitochondrial channel blocker, antimycin A (6.25 µM), for 12 h to induce mitochondrial dysfunction. Thereafter, cells were treated with aspalathin, isoorientin, and orientin (10 µM) for 4 h, while metformin (1 µM) and insulin (1 µM) were used as comparators. Relevant bioassays and real-time PCR were conducted to assess the impact of treatment compounds on some markers of mitochondrial function. Our results showed that antimycin A induced alterations in the mitochondrial respiration process and mRNA levels of genes involved in energy production. In fact, aspalathin, isoorientin, and orientin reversed such effects leading to the reduced production of intracellular reactive oxygen species. These flavonoids further enhanced the expression of genes involved in mitochondrial function, such as Ucp 2, Complex 1/3, Sirt 1, Nrf 1, and Tfam. Overall, the current study showed that dietary flavonoids, aspalathin, isoorientin, and orientin, have the potential to be as effective as established pharmacological drugs such as metformin and insulin in protecting against mitochondrial dysfunction in a preclinical setting; however, such information should be confirmed in well-established in vivo disease models.

Antimycin A-induced mitochondrial dysfunction is consistent with impaired insulin signaling in cultured skeletal muscle cells.

Insulin resistance and mitochondrial dysfunction are characteristic features of type 2 diabetes mellitus. However, a causal relationship between insulin resistance and mitochondrial dysfunction has not been fully established in the skeletal muscle. Accordingly, we have evaluated the effect of antimycin A (AA), a mitochondrial electron transport chain complex III inhibitor, on mitochondrial bioenergetics and insulin signaling by exposing C2C12 skeletal muscle cells to its concentrations of 3.125, 6.25, 12.5, 25, and 50 µM for 12 h. Thereafter, metabolic activity, ROS production, glucose uptake, Seahorse XF Real-time ATP and Mito Stress assays were performed. Followed by real-time polymerase chain reaction (RT-PCR) and Western blot analysis. This study confirmed that AA induces mitochondrial dysfunction and promote ROS production in C2C12 myotubes, culminating in a significant decrease in mitochondrial respiration and downregulation of genes involved in mitochondrial bioenergetics (TFAM, UCP2, PGC1α). Increased pAMPK and extracellular acidification rates (ECAR) confirmed a potential compensatory enhancement in glycolysis. Additionally, AA impaired insulin signaling (protein kinase B/AKT) and decreased insulin stimulated glucose uptake. This study confirmed that an adaptive relationship exists between mitochondrial functionality and insulin responsiveness in skeletal muscle. Thus, therapeutics or interventions that improve mitochondrial function could ameliorate insulin resistance as well.

The Potential Role of Polyphenols in Modulating Mitochondrial Bioenergetics within the Skeletal Muscle: A Systematic Review of Preclinical Models.

Polyphenols are naturally derived compounds that are increasingly being explored for their various health benefits. In fact, foods that are rich in polyphenols have become an attractive source of nutrition and a potential therapeutic strategy to alleviate the untoward effects of metabolic disorders. The last decade has seen a rapid increase in studies reporting on the bioactive properties of polyphenols against metabolic complications, especially in preclinical models. Various experimental models involving cell cultures exposed to lipid overload and rodents on high fat diet have been used to investigate the ameliorative effects of various polyphenols against metabolic anomalies. Here, we systematically searched and included literature reporting on the impact of polyphenols against metabolic function, particularly through the modulation of mitochondrial bioenergetics within the skeletal muscle. This is of interest since the skeletal muscle is rich in mitochondria and remains one of the main sites of energy homeostasis. Notably, increased substrate availability is consistent with impaired mitochondrial function and enhanced oxidative stress in preclinical models of metabolic disease. This explains the general interest in exploring the antioxidant properties of polyphenols and their ability to improve mitochondrial function. The current review aimed at understanding how these compounds modulate mitochondrial bioenergetics to improve metabolic function in preclinical models on metabolic disease.

The triterpene, methyl-3ß-hydroxylanosta-9,24-dien-21-oate (RA3), attenuates high glucose-induced oxidative damage and apoptosis by improving energy metabolism.

BACKGROUND: Hyperglycemia-induced cardiovascular dysfunction has been linked to oxidative stress and accelerated apoptosis in the diabetic myocardium. While there is currently no treatment for diabetic cardiomyopathy (DCM), studies suggest that the combinational use of anti-hyperglycemic agents and triterpenes could be effective in alleviating DCM. HYPOTHESIS: To investigate the therapeutic effect of methyl-3ß-hydroxylanosta-9,24-dien-21-oate (RA3), in the absence or presence of the anti-diabetic drug, metformin (MET), against hyperglycemia-induced cardiac injury using an in vitro H9c2 cell model. METHODS: To mimic a hyperglycemic state, H9c2 cells were exposed to high glucose (HG, 33 mM) for 24 h. Thereafter, the cells were treated with RA3 (1 µM), MET (1 µM) and the combination of MET (1 µM) plus RA3 (1 µM) for 24 h, to assess the treatments therapeutic effect. RESULTS: Biochemical analysis revealed that RA3, with or without MET, improves glucose uptake via insulin-dependent (IRS-1/PI3K/Akt signaling) and independent (AMPK) pathways whilst ameliorating the activity of antioxidant enzymes in the H9c2 cells. Mechanistically, RA3 was able to alleviate HG-stimulated oxidative stress through the inhibition of reactive oxygen species (ROS) and lipid peroxidation as well as the reduced expression of the PKC/NF-кB cascade through decreased intracellular lipid content. Subsequently, RA3 was able to mitigate HG-induced apoptosis by decreasing the activity of caspase 3/7 and DNA fragmentation in the cardiomyoblasts. CONCLUSION: RA3, in the absence or presence of MET, demonstrated potent therapeutic properties against hyperglycemia-mediated cardiac damage and could be a suitable candidate in the prevention of DCM.

The effect of adiponectin in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and the potential role of polyphenols in the modulation of adiponectin signaling.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, as it affects up to 30 % of adults in Western countries. Moreover, NAFLD is also considered an independent risk factor for cardiovascular diseases. Insulin resistance and inflammation have been identified as key factors in the pathophysiology of NAFLD. Although the mechanisms associated with the development of NAFLD remain to be fully elucidated, a complex interaction between adipokines and cytokines appear to play a crucial role in the development of this condition. Adiponectin is the most common adipokine known to be inversely linked with insulin resistance, lipid accumulation, inflammation and NAFLD. Consequently, the focus has been on the use of new therapies that may enhance hepatic expression of adiponectin downstream targets or increase the serum levels of adiponectin in the treatment NAFLD. While currently used therapies show limited efficacy in this aspect, accumulating evidence suggest that various dietary polyphenols may stimulate adiponectin levels, offering potential protection against the development of insulin resistance, inflammation and NAFLD as well as associated conditions of metabolic syndrome. As such, this review provides a better understanding of the role polyphenols play in modulating adiponectin signaling to protect against NAFLD. A brief discussion on the regulation of adiponectin during disease pathophysiology is also covered to underscore the potential protective effects of polyphenols against NAFLD. Some of the prominent polyphenols described in the manuscript include aspalathin, berberine, catechins, chlorogenic acid, curcumin, genistein, piperine, quercetin, and resveratrol.

Isoorientin ameliorates lipid accumulation by regulating fat browning in palmitate-exposed 3T3-L1 adipocytes.

Stimulation of fat browning using natural bioactive products is regarded as one of the promising approaches to treat obesity and insulin resistance. Here, we investigated the physiological effects of isoorientin on glucose uptake and lipid accumulation in insulin resistant 3T3-L1 adipocytes. To achieve this, 3T3-L1 adipocytes were exposed to 0.75 mM palmitate for 24 h, to induce insulin resistance, before treatment with 10 µM isoorientin or the comparative controls such as CL-316,243 (10 µM), pioglitazone (10 µM) and compound C (1 µM) for 4 h. Relevant bioassays and Western blot analysis were conducted on these insulin resistant cells. Our results showed that palmitate exposure could induce insulin resistance and mitochondrial dysfunction as measured by reduction in glucose uptake and impaired mitochondrial bioenergetics parameters. However, treatment with isoorientin reversed these effects by improving glucose uptake, blocking lipid accumulation, and modulating the process of mitochondrial respiration. Mechanistically, isoorientin could mediate lipid metabolism by activating 5' AMP-activated protein kinase (AMPK), while also effectively modulating the expression of genes involved in fat browning such as peroxisome proliferator-activated receptor gamma (PPAR)γ/α and uncoupling protein 1 (UCP1). In conclusion, isoorientin impacts insulin resistance in vitro by improving glucose uptake and mitochondrial function, consistent to modulating the expression of genes involved in energy metabolism and fat browning.

Effect of Solanum macrocarpon Linn leaf aqueous extract on the brain of an alloxan-induced rat model of diabetes.

OBJECTIVE: This study was designed to evaluate the protective effect of aqueous extract of Solanum macrocarpon Linn leaf in the brain of an alloxan-induced rat model of diabetes. METHODS: The experimental model of diabetes was induced by a single intraperitoneal injection of freshly prepared alloxan. Rats were then divided into six groups: normal control, diabetes control, diabetes group treated with metformin, and three diabetes groups treated with different concentrations of S. macrocarpon. Rats were sacrificed on day 14 of the experiment and different brain biochemical parameters were assessed and compared between groups. RESULTS: Administration of different doses of S. macrocarpon leaf aqueous extract was associated with significantly reduced levels of fasting blood glucose, lipid peroxidation, neurotransmitters, cholinesterases, cyclooxygenase-2 and nitric oxide compared with diabetes control rats. In addition, antioxidant enzyme activities were significantly increased in diabetes rats administered 12.45, 24.9 and 49.8 mg/kg body weight of S. macrocarpon versus diabetes control rats. CONCLUSION: Aqueous extract of S. macrocarpon Linn leaf may be useful in the management of diabetic neuropathy.

Isoorientin: A dietary flavone with the potential to ameliorate diverse metabolic complications.

Isoorientin is a natural C-glucosyl flavone that is generating a lot of interest due to its multiple pharmacological activities. Increasing experimental data have shown that the robust antioxidant and anti-inflammatory properties of isoorientin remain important in ameliorating a number of metabolic complications. In fact, plants rich in isoorientin have demonstrated strong ameliorative properties against complications such as hyperglycemia, hyperlipidemia, and insulin resistance. However, while such evidence is accumulating, it has not been reviewed to better inform on the therapeutic potential of this flavone in improving human health. This review examines and extrapolates available literature on the potential beneficial or detrimental effects associated with the use of isoorientin in mitigating metabolic diseases, with a specific focus on diabetes, obesity, and insulin resistance, including associated complications. The discussion includes effective doses in various experimental settings and proposed molecular mechanisms by which isoorientin may exert its therapeutic effects. In addition, the protective effects of extracts of a number of isoorientin-rich plants against metabolic complications will be highlighted.

Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes.

The current study explored the effect of isoorientin on the metabolic activity and lipid accumulation in fully differentiated 3T3-L1 adipocytes. To achieve this, the 3T3-L1 pre-adipocytes were differentiated for eight days and treated with various concentrations of isoorientin (0.1-100 µM) for four hours. Subsequently, the metabolic activity, lipid accumulation, and mitochondrial respiration were assessed. Furthermore, to unravel the molecular mechanisms that might elucidate the bioactivity of isoorientin, protein expression of the genes involved in insulin signaling and energy expenditure, such as AKT and AMPK, were investigated. The results showed that isoorientin, at different doses, could block lipid storage and enhance glycerol release, with a concomitant improvement of the metabolic activity and mitochondrial function. Although the observed beneficial effects of isoorientin on these cultured 3T3-L1 adipocytes were not consistent at all concentrations, it was clear that doses between 1 and 10 µM were most effective compared to the untreated control. Moreover, the activity of isoorientin was comparable to tested positive controls of CL-316,2431, isoproterenol, insulin, and metformin. Mechanistically, protein expression of AKT and AMPK, was enhanced with isoorientin exposure, suggesting their partial role in modulating lipid metabolism and mitochondrial biogenesis. Indeed, our results showed that isoorientin has the ability to enhance mitochondrial respiration, as we observed an increase in the ATP and oxygen consumption rate. Therefore, we concluded that isoorientin has a potential to impact mitochondrial activity, lipid metabolism and energy expenditure using an in vitro experimental model of obesity.

An In Vitro Study on the Combination Effect of Metformin and N-Acetyl Cysteine against Hyperglycaemia-Induced Cardiac Damage.

Chronic hyperglycaemia is a major risk factor for diabetes-induced cardiovascular dysfunction. In a hyperglycaemic state, excess production of reactive oxygen species (ROS), coupled with decreased levels of glutathione, contribute to increased lipid peroxidation and subsequent myocardial apoptosis. N-acetylcysteine (NAC) is a thiol-containing antioxidant known to protect against hyperglycaemic-induced oxidative stress by promoting the production of glutathione. While the role of NAC against oxidative stress-related cardiac dysfunction has been documented, to date data is lacking on its beneficial effect when used with glucose lowering therapies, such as metformin (MET). Thus, the aim of the study was to better understand the cardioprotective effect of NAC plus MET against hyperglycaemia-induced cardiac damage in an H9c2 cardiomyoblast model. H9c2 cardiomyoblasts were exposed to chronic high glucose concentrations for 24 h. Thereafter, cells were treated with MET, NAC or a combination of MET and NAC for an additional 24 h. The combination treatment mitigated high glucose-induced oxidative stress by improving metabolic activity i.e. ATP activity, glucose uptake (GU) and reducing lipid accumulation. The combination treatment was as effective as MET in diminishing oxidative stress, lipid peroxidation and apoptosis. We observed that the combination treatment prevented hyperglycaemic-induced cardiac damage by increasing GLUT4 expression and mitigating lipid accumulation via phosphorylation of both AMPK and AKT, while decreasing nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), as well as protein kinase C (PKC), a known activator of insulin receptor substrate-1 (IRS-1), via phosphorylation at Ser307. On this basis, the current results support the notion that the combination of NAC and MET can shield the diabetic heart against impaired glucose utilization and therefore its long-term protective effect warrants further investigation.

Antihyperglycaemia and related gene expressions of aqueous extract of Gongronema latifolium leaf in alloxan-induced diabetic rats.

Context: Gongronema latifolium Benth (Asclepiadaceae) has been highly utilized in controlling diabetes mellitus traditionally in the eastern part of Nigeria. Objectives: Antihyperglycaemic and related gene expressions of aqueous extract of Gongronema latifolium leaf in alloxan-induced diabetic rats. Materials and methods: Forty-eight female Wistar rats were induced intraperitoneally using alloxan (150 mg/kg body weight). The rats were separated into six groups (n = 8) as follows: non-diabetic control, diabetic control, diabetic rats administered 5 mg/kg body weight of metformin, and diabetic rats administered 6.36, 12.72 and 25.44 mg/kg body weight (ethnobotanical doses) of G. latifolium orally daily. On the 14th day, the animals were sacrificed and different antihyperglycaemic parameters were evaluated as well as its related gene expressions. Results: Diabetic rats administered three doses of aqueous extract of G. latifolium significantly (p < 0.05) lowered the fasting blood glucose, glycated haemoglobin, serum lipid profiles, lipid peroxidation (5.62-1.2 µ/mg protein) levels, as well as gene expression of glucose-6-phosphatase in alloxan-induced diabetic rats. There was a significant (p < 0.05) increase in the liver glycogen content (16.23-112.5 mg glucose/2 g), antioxidant enzymes activities, glucose transporter (GLUT-2 and GLUT-4) levels and relative gene expression of hexokinase in diabetic rats administered different doses of aqueous extract of G. latifolium. Discussion and conclusions: It can be deduced that the aqueous extract of G. latifolium leaf at these doses may be useful in managing diabetes mellitus and its associated complications. Therefore, this extract may be a potent antidiabetic agent in clinical therapy in the future.

Interplay between heat shock proteins, inflammation and cancer: a potential cancer therapeutic target.

The historical relationship between cancer and inflammation has long been evaluated, and dates back to the early work of Virchow (1863), where he hypothesised that chronic inflammation as a direct cause of tissue injury and infection, could actually promote tissue proliferation. At that period in time however, the exact mechanisms that mediated this relationship were little understood. Subsequent studies have since then demonstrated that chronic inflammation plays significant roles in microenvironments, mostly in the progression of tumours, probably, through over-secretion of proinflammatory cytokines and other immune-killing apparatus such as reactive oxygen species (ROS) which cause damage to normal cells leading to DNA damage and increased cellular mutation rates. Recently, the identification of DNA lesion 5-chlorocytosine (5-CIC) created by hypochlorous acid (HOCl) secreted to nullify or kill infectious agents and toll-like receptor 4 (TLR4)-mediated chronic inflammation in the human gut, has become the latest evidence linking inflammation directly to cancer. The key to cellular survival and adaptation under unfavourable or pathological conditions is the expression of heat shock proteins (HSPs) also called molecular chaperones. These proteins play essential roles in DNA repair processes by maintaining membrane integrity, orderliness and stability of client proteins that play prominent roles in DNA repair mechanisms. More so, HSPs have also been shown to modulate the effects of pro-inflammatory/apoptotic cytokines through the inhibition of cascades leading to the generation of ROS-mediated DNA damage, while promoting the DNA repair mechanism, thus playing prominent roles in various stages of DNA repair and cancer progression. Hence, studies targeting HSPs and their inhibitors in inflammation, DNA damage, and repair, could improve current cancer therapeutic efficiency. Here the focus will be on the relationship between HSPs, inflammation and cancer, as well as roles of HSPs in DNA damage response (DDR).

Lanosteryl triterpenes from Protorhus longifolia as a cardioprotective agent: a mini review.

The epidemic of cardiovascular diseases is a global phenomenon that is exaggerated by the growing prevalence of diabetes mellitus. Coronary artery disease and diabetic cardiomyopathy are the major cardiovascular complications responsible for exacerbated myocardial infarction in diabetic individuals. Increasing research has identified hyperglycemia and hyperlipidemia as key factors driving the augmentation of oxidative stress and a pro-inflammatory response that usually results in increased fibrosis and reduced cardiac efficiency. While current antidiabetic agents remain active in attenuating diabetes-associated complications, overtime, their efficacy proves limited in protecting the hearts of diabetic individuals. This has led to a considerable increase in the number of natural products that are screened for their antidiabetic and cardioprotective properties. These natural products may present essential ameliorative properties relevant to their use as a monotherapy or as an adjunct to current drug agents in combating diabetes and its associated cardiovascular complications. Recent findings have suggested that triterpenes isolated from Protorhus longifolia (Benrh.) Engl., a plant species endemic to Southern Africa, display strong antioxidant and antidiabetic properties that may potentially protect against diabetes-induced cardiovascular complications. Thus, in addition to discussing the pathophysiology associated with diabetes-induced cardiovascular injury, available evidence pertaining to the cardiovascular protective potential of lanosteryl triterpenes from Protorhus longifolia will be discussed.

Aspalathin ameliorates doxorubicin-induced oxidative stress in H9c2 cardiomyoblasts.

Aspalathin (ASP) is a C-dihydrochalcone abundantly found in Aspalathus linearis. While we have provide evidence that ASP can protect H9c2 cardiomyoblasts against doxorubicin (Dox)-induced apoptosis through regulation of autophagy, the complete mechanism involved in the cardioprotective effect of this dihydrochalcone remains to be explored. Here we provide evidence that ASP reverses Dox-induced apoptosis through the amelioration of oxidative stress in H9c2 cardiomyoblasts. Cultured cells were treated with 0.2 µM Dox or co-treated with either 20 µM dexrazoxane (Dexra) or 0.2 µM ASP daily for five days, to a final dose of 1 µM Dox, 100 µM Dexra and 1 µM ASP, respectively. Superoxide dismutase, catalase, glutathione, malondialdehyde and dichloro-dihydro-fluorescein diacetate fluorescence were used as end-point measurements for oxidative stress, while JC-1 and TUNEL labeling were performed to assess mitochondria depolarization and apoptosis. Co-treatment with ASP attenuated Dox-induced cardiotoxicity by improving endogenous antioxidant levels and mitochondrial membrane potential, while inhibiting reactive oxygen species production and cellular apoptosis. These findings suggested that ASP can prevent Dox-induced oxidative stress and apoptosis and needs further assessment to confirm its therapeutic potential to prevent Dox-induced cardiotoxicity.

Comparative study on proximate, functional, mineral, and antinutrient composition of fermented, defatted, and protein isolate of Parkia biglobosa seed.

The use of plant-derived foods in the prevention, treatment, and management of metabolic diseases especially diabetes has gained prominence; this has been associated with their physicochemical properties. This study was conducted to compare the proximate, functional, mineral, and antinutrient composition of the fermented seeds, the defatted seeds, and the protein isolate from Parkia biglobosa seeds. The results showed that the fermented, defatted, and protein isolate varied in composition within the parameters studied. The proximate analysis revealed that the protein isolate had the highest ash (6.0%) and protein (59.4%) as well as the lowest fat (5.7%) and moisture (5.1%) content when compared to the fermented and defatted samples. In like manner, the functional properties of the protein isolate were relatively better than those of the fermented and defatted samples, with oil absorption capacity of 4.2% and emulsion capacity of 82%. The magnesium and zinc content of the protein isolate were significantly higher when compared with the fermented and defatted samples, while a negligible amount of antinutrient was present in all the samples, with the protein isolate having the lowest quantity. The overall data suggest that the protein isolate had better proximate, mineral, functional, and antinutrient properties when compared to the fermented and defatted samples. Therefore, the synergistic effect of all these components present in the protein isolate from P. biglobosa seed in association with its low carbohydrate and high protein/ash contents could play a vital role in the management of diabetes and its associated complications.