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Abstract Beta vulgaris L. is a root vegetable that is consumed mainly as a food additive. This study aimed to describe the protective effect of B. vulgaris on Fe2+-mediated oxidative liver damage through in vitro, ex vivo, and in silico studies to establish a strong rationale for its protective effect. To induce oxidative damage, we incubated the livers of healthy male rats with 0.1 mM FeSO4 to induce oxidative injury and coincubated them with an aqueous extract of B. vulgaris root (BVFE) (15–240 µg/mL). Induction of liver damage significantly (p

Infertility has become a significant health burden around the globe as it is believed that 15 % of married couples struggle with infertility, with half of the problem accrued to the male. The issue of male infertility could be traced to insufficient or absence of spermatozoa. Glucose metabolism is essential for continued spermatogenesis and for the reproductive potential of sperm cells. Appropriate nutrition is critical in maintaining reproductive function as caloric restriction along with weight reduction, excessive food consumption and obesity are harmful to reproductive function. The link between metabolism and reproduction is tied to metabolic hormones like insulin, leptin and thyroid, extracellular environment, mitochondria function, nutrient substrate, availability, and environmental stressors. Although matured spermatozoa utilize glucose directly, it is not the preferred energy substrate for germ cells as they rely on Sertoli cells to supply lactate. The reproductive potential of sperm cells depends on certain modifications like hyperactivated motility, which is mainly dependent on glucose metabolism. Without other energy sources, spermatozoa utilize their internal lipid stores. The uptake and metabolism of glucose by sperm are essential endpoints for determining the potential fertility of male individuals. The biological energy in sperm cells fuels all the physiological processes they engage in, from their deposition in the female reproductive tract to the point where they fertilize an egg. This article thus reviews facts pertinent to the energy metabolism of male germ cells and Sertoli cells.

SDN controllers are increasingly becoming an integral part of modern communication networks due to their ability to centrally control and manage networks from a global point of view. One of the application areas in which the SDN paradigm is gaining traction is the Integration of Satellite and Terrestrial Networks (ISTN). Considering that there are different SDN controllers with their intrinsic characteristics, which translate to different performance characteristics, it is pertinent to determine the SDN controllers that will be most suitable for the specific application area. This study embarked on evaluating selected SDN controllers that will help in making informed selection decisions for suitability in a future ISTN architecture. Five SDN controllers were subjected to evaluation and they are Open Network Operating System (ONOS), Opendaylight (ODL), Floodlight (FL), Ryu, and Pox. These controllers are evaluated based on throughput and latency metrics, which are considered some of the factors that could influence the performance of the interworking of both terrestrial and satellite networks. The controllers were subjected under various topologies and traffic densities which are (i) single topologies under no cross traffic, half-bandwidth cross traffic, and high-bandwidth cross traffic conditions (ii) linear topology under no cross traffic, half-bandwidth cross traffic, and high-bandwidth cross traffic conditions (iii) tree topology under no cross traffic, half-bandwidth cross traffic, and high-bandwidth cross traffic conditions (ii) linear topology under no cross traffic, half-bandwidth cross traffic, and high-bandwidth cross traffic conditions (iii) tree topology under no cross traffic, half-bandwidth cross traffic, and high-bandwidth cross traffic conditions. Under all conditions, ONOS shows superiority in terms of throughput while Ryu shows superiority in terms of synchronization time. Focusing specifically on the tree topologies, considering it follows the same pattern with the single and linear topologies, the ONOS exhibited throughput of 815flow/ms under no cross traffic and throughput of 807flow/ms under both half-bandwidth and high-bandwidth band cross traffic. Ryu exhibited a synchronisation time of 19ms, 23ms, and 26ms under the no cross traffic, half-bandwidth cross traffic, and high-bandwidth traffic cross-traffic conditions, respectively. Observing from the values for both the throughput and synchronisation time metrics under all the topologies, it can be inferred that a number of hosts have more impact on the metrics rather than traffic volume, and this could be attributed to caching mechanisms like Address Resolution Protocol (ARP) wherein new traffic from known hosts can quickly be processed compared to new traffic from new hosts. In summary, the ONOS controller can be considered to offer good performance in an ISTN.

The mitophagy process, a type of macroautophagy, is the targeted removal of mitochondria. It is a type of autophagy exclusive to mitochondria, as the process removes defective mitochondria one by one. Mitophagy serves as an additional level of quality control by using autophagy to remove superfluous mitochondria or mitochondria that are irreparably damaged. During spermatogenesis, mitophagy can influence cell homeostasis and participates in a variety of membrane trafficking activities. Crucially, it has been demonstrated that defective mitophagy can impede spermatogenesis. Despite an increasing amount of evidence suggesting that mitophagy and mitochondrial dynamics preserve the fundamental level of cellular homeostasis, little is known about their role in developmentally controlled metabolic transitions and differentiation. It has been observed that male infertility is a result of mitophagy's impact on sperm motility. Furthermore, certain proteins related to autophagy have been shown to be present in mammalian spermatozoa. The mitochondria are the only organelle in sperm that can produce reactive oxygen species and finally provide energy for sperm movement. Furthermore, studies have shown that inhibited autophagy-infected spermatozoa had reduced motility and increased amounts of phosphorylated PINK1, TOM20, caspase 3/7, and AMPK. Therefore, in terms of reproductive physiology, mitophagy is the removal of mitochondria derived from sperm and the following preservation of mitochondria that are exclusively maternal.

This work presents an improved cuckoo search algorithm based on Success Rate (CSA-SR) for optimal allocation of Distributed Generation (DG). This is necessary in order to improve the power quality of the distribution system by minimizing power loss and improving voltage stability. Voltage Stability Index (VSI) is applied to identify restricted unhealthy buses/areas in the distribution networks. The work is implemented on standard IEEE 33 Bus test systems. Newton Raphson Power Flow (NRPF) technique is used in MATLAB R2019b environment for the power flow analysis. The overall IEEE 33 Bus system real power loss obtained from the simulation result is found to be 202.7071MW at the base case. Following the application of 3 DGs using CSA-SR, the real power loss is found to be 113.9630 MW which shows a reduction of 88.441MW which is equivalent to 43.77% as related to the base case. The results minimized the system losses while significantly enhancing the voltage profile of the bus voltages as a result of optimal siting and sizing of the DG. These show that the CSA-SR technique outperformed PSO, which was used to ascertain the effectiveness of the developed scheme.

Infertility has been a major issue in our society for many years, and millions of couples all over the world are still experiencing it. There are several reasons for and causes of infertility in both men and women. Recent studies have shown that apoptosis, inflammation, and oxidative stress contribute immensely to infertility. The data regarding this report were obtained through a thorough review of scientific articles published in various databases, including Elsevier, Web of Science, PubMed, Scopus, and Google Scholar. Furthermore, PhD and MSc theses were also reviewed when compiling the data. Apoptosis, also known as ''programmed cell death,'' is a natural and harmless process that occurs in human beings. Although it can become harmful if altered, Inflammation, on the other hand, is the body’s reaction to detrimental stimuli caused by toxic substances or compounds, while oxidative stress is a phenomenon that results in an imbalance between the generation and aggregation of reactive oxygen species (ROS) in the cells against antioxidants. These three factors interchangeably bring about several reproductive disorders in the body, resulting in infertility. This review aims at discussing how apoptosis, inflammation, and oxidative stress play a role in human infertility. Availability of data and material: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Introduction: This study aimed to investigate the chemical profile of GC-MS, antioxidant, anti-diabetic, and anti-inflammatory activities of the ethyl acetate fraction of Spilanthes filicaulis leaves (EFSFL) via experimental and computational studies.Methods: After inducing oxidative damage with FeSO4, we treated the tissues with different concentrations of EFSFL. An in-vitro analysis of EFSFL was carried out to determine its potential for antioxidant, anti-diabetic, and anti-inflammatory activities. We also measured the levels of CAT, SOD, GSH, and MDA.Results and discussion: EFSFL exhibited anti-inflammatory properties through membrane stabilizing properties (IC50 = 572.79 μg/ml), proteinase inhibition (IC50 = 319.90 μg/ml), and inhibition of protein denaturation (IC50 = 409.88 μg/ml). Furthermore, EFSFL inhibited α-amylase (IC50 = 169.77 μg/ml), α-glucosidase (IC50 = 293.12 μg/ml) and DPP-IV (IC50 = 380.94 μg/ml) activities, respectively. Our results indicated that induction of tissue damage reduced the levels of GSH, SOD, and CAT activities, and increased MDA levels. However, EFSFL treatment restores these levels to near normal. GC-MS profiling shows that EFSFL contains 13 compounds, with piperine being the most abundant. In silico interaction of the phytoconstituents using molecular and ensembled-based docking revealed strong binding tendencies of two hit compounds to DPP IV (alpha-caryophyllene and piperine with a binding affinity of −7.8 and −7.8 Kcal/mol), α-glucosidase (alpha-caryophyllene and piperine with a binding affinity of −9.6 and −8.9 Kcal/mol), and to α-amylase (piperine and Benzocycloheptano[2,3,4-I,j]isoquinoline, 4,5,6,6a-tetrahydro-1,9-dihydroxy-2,10-dimethoxy-5-methyl with a binding affinity of −7.8 and −7.9 Kcal/mol), respectively. These compounds also presented druggable properties with favorable ADMET. Conclusively, the antioxidant, antidiabetic, and anti-inflammatory activities of EFSFL could be due to the presence of secondary metabolites.

The purpose of this study was to investigate the protective effect of Beta vulgaris leaf extract (BVLE) on Fe2+-induced oxidative testicular damage via experimental and computational models. Oxidative testicular damage was induced via incubation of testicular tissue supernatant with 0.1 mM FeSO4 for 30 min at 37 °C. Treatment was achieved by incubating the testicular tissues with BVLE under the same conditions. The catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) levels, acetylcholinesterase (AChE), sodium-potassium adenosine triphosphatase (Na+/K + ATPase), ecto-nucleoside triphosphate diphosphohydrolase (ENTPDase), glucose-6-phosphatase (G6Pase), and fructose-1,6-bisphosphatase (F-1,6-BPase) were all measured in the tissues. We identified the bioactive compounds present using high-performance liquid chromatography (HPLC). Molecular docking and dynamic simulations were done on all identified compounds using a computational approach. The induction of testicular damage (p

This study aimed to examine the therapeutic activity of the cinnamic acid derivative KAD-7 (N′-(2,4-dichlorobenzylidene)-3-(4-methoxyphenyl) acrylohydrazide) on Fe2+-induced oxidative hepatic injury via experimental and computational models. In addition, the role of ATPase and ectonucleoside triphosphate diphosphohydrolase (ENTPDase) in the coordination of cellular signals is speculated upon to proffer suitable therapeutics for metabolic stress disorder upon their inhibition. While we know little about therapeutics with flexible dual inhibitors for these protein targets, this study was designed to screen KAD-7’s (N′-(2,4-dichlorobenzylidene)-3-(4-methoxyphenyl) acrylohydrazide) inhibitory potential for both protein targets. We induced oxidative hepatic damage via the incubation of hepatic tissue supernatant with 0.1 mM FeSO4 for 30 min at 37 °C. We achieved the treatment by incubating the hepatic tissues with KAD-7 under the same conditions. The catalase (CAT), glutathione (GSH), malondialdehyde (MDA), ATPase, and ENTPDase activity were all measured in the tissues. We predicted how the drug candidate would work against ATPase and ENTPDase targets using molecular methods. When hepatic injury was induced, there was a significant decrease in the levels of the GSH, CAT, and ENTPDase (p < 0.05) activities. In contrast, we found a noticeable rise in the MDA levels and ATPase activity. KAD-7 therapy resulted in lower levels of these activities overall (p < 0.05), as compared to the control levels. We found the compound to have a strong affinity for ATPase (−7.1 kcal/mol) and ENTPDase (−7.4 kcal/mol), and a better chemical reactivity than quercetin. It also met all drug-likeness parameters. Our study shows that KAD-7 can protect the liver from damage caused by FeSO4 by reducing oxidative stress and purinergic actions. Our studies indicate that KAD-7 could be developed as a therapeutic option since it can flexibly inhibit both ATPase and ENTPDase.

This work focuses on the clustering in Wireless Body Area Network (WBAN). Recently, it was found that less attention was given to Line-of-Sight (LoS) and Non-Line-of-Sight (NLoS) clustering in WBAN. Past works on LoS clustering WBAN consider the problem of enhancing the network throughput and end-to-end delay of the network. However, the problem of necessary hop count for packet transmission has not been considered. The non-consideration of necessary nodes hop count degrades the performance of cluster-based WBAN as throughput of the network is reduced in addition to high end-to-end delay. This work develops a hop count aware WBAN for enhancing the performance of body nodes called improved Dual Sink Approach using Clustering in Body Area Network (iDSCB). The simulation results depicted that the hop distance criterion of iDCSB improved the performance of WBAN in terms of end-to-end delay and throughput by 3.16% and 6.59%, respectively.

Abstract The treatment of diabetes involves the use of herbal plants, attracting interest in their cost-effectiveness and efficacy. An aqueous extract of Persea americana seeds (AEPAS) was explored in this study as a possible therapeutic agent in rats with diabetes mellitus. The induction of diabetes in the rats was achieved by injecting 65 mg/kg body weight (BWt) of alloxan along with 5% glucose. This study was conducted using thirty-six (36) male Wistar rats. The animals were divided into 6 equal groups, (n = 6) and treated for 14 days. In vitro assays for total flavonoid, phenols, FRAP, DPPH, NO, α-amylase, and α-glucosidase, were performed. Biochemical indices fasting blood sugar (FBS), BWt, serum insulin, liver hexokinase, G6P, FBP, liver glycogen, IL-6, TNF-α, and NF-ĸB in the serum, were investigated as well as the mRNA expressions of PCNA, Bcl2, PI3K/Akt in the liver and pancreas. The in vitro analyses showed the potency of AEPAS against free radicals and its enzyme inhibitory potential as compared with the positive controls. AEPAS showed a marked decrease in alloxan-induced increases in FBG, TG, LDL-c, G6P, F-1, 6-BP, MDA, IL-6, TNF-α, and NF-ĸB and increased alloxan-induced decreases in liver glycogen, hexokinase, and HDL-c. The diabetic control group exhibited pancreatic dysfunction as evidenced by a reduction in serum insulin, HOMA-β, expressions of PI3K/AKT, Bcl-2, and PCNA combined with an elevation in HOMA-IR. The HPLC revealed luteolin and myricetin to be the phytochemicals that were present in the highest concentration in AEPAS. The outcome of this research showed that the administration of AEPAS can promote the activation of the PI3K/AkT pathway and the inhibition of β-cell death, which may be the primary mechanism by which AEPAS promotes insulin sensitivity and regulates glycolipid metabolism.

Wireless body area networks (WBANs) assemble multiple transceiver nodes in, on, or around a patient's body to transmit physiological signals to the sink node and further send it to the medical personnel via a medical server. WBANs a sensor network that is characterized as energy-dependent. Due to this finite nature, the deployment of intelligent utilization is needed. Quality of service (QoS) is another area that needs rapt attention to receive exactly what was sent from the source node to the destination node and throughput. Critical data transmission is characterized by abnormal data status that requires an urgent response from the medical personnel without delay to save the patient's life. In this review article, we propose a review of critical data transmission in wireless body area networks. However, most past articles in this line focus more on energy-efficient, security and privacy, quality of the links, throughput, network maximization, and so on. None of them looks into the direction of transmitting critical data directly to the sink node without multi-hopping of the physiological signals between intermediate nodes, which wastes the time of transmission to save patient life. This disparity between these scholars motivates us to fill the gap between them. This review article briefly discussed the state-of-the-art critical data transmission in WBANs alongside the WBANs architecture and implementation. Furthermore, a pragmatic approach to determining the threshold's degree of critical data index sensed during transmission was also considered.

Wireless Body Area Networks (WBANs) are an integral part of a Wireless sensor network, where sensor nodes are strategically placed in the human body to sense physiological signals and transmit them to the medical personnel via server for medical observations. Every sensor node in WBANs has a general limitation in energy efficiency, end-to-end delay, residual energy, etc. Also, the high energy consumption in WBANs is mainly due to the number of hops covered during physiological signal transmission. This work developed a hop-distance scenario to address these challenges and improve on what others have done. It buffered traffic estimation schemes to minimize end-to-end delay and the total network energy efficiency. This work minimizes end-to-end delay dual-sink cluster-based routing in WBANs by improving the existing dual-sink-sink cluster-based scheme (iDSCB). The simulation result shows that the Minimization of end-to-end delay of the improved dual-sink cluster-based (iDSCB) enhanced the performance of the current article DSCB in terms of end-to-end delay and residual energy by 3.15% and 8.88%, respectively.

WBAN comprises multiple sensor nodes strategically located on patients' bodies. They collect physiological signals from a patient under medical observation and transmit them to the medical personnel for further analysis via a medical server. These sensor nodes are energy-dependent. The challenges associated with WBAN are the power source, delay, and so on. Since their energy source is derived from rechargeable batteries, it is impossible to stop the network operation to replace the battery. Past articles concentrated more on the problem of enhancing network delay and throughput. However, they did not look into the area of TDMA and CCA schemes to improve their work. This brings their work into network energy degradation, which reduces their throughput. This article implements Enhancing throughput cluster-based DSCB by improving the existing Dual-sink clustering approach (DSCB). The simulation result depicted that the Enhanced throughput of iDSCB improved the performance of the current work DSCB in terms of throughput and End-to-End Delay by 6.60% and 3.14%, respectively.

Background: The genus Pennisetum contains remarkable natural bioactive components, and its 140 species are widely distributed in tropical and subtropical countries, where they are frequently used for therapeutic purposes such as the treatment of dysentery, fever, diabetes, and abdominal pain by indigenous people. However, the available information for this genus has not been thoroughly researched in terms of their bioactive principles and extracts. Aim of the review: The current review provides a profound perception, enhanced understanding, and comprehensive information on the traditional uses, phytochemical compounds, and biological activities of the genus Pennisetum, as well as toxicological perspectives. Furthermore, the significance of ethnopharmacological uses, application, and the beneficial potential of Pennisetum species for the management of a variety of diseases were thoroughly discussed. Materials and methods: The significant data of Pennisetum species was obtained through a thorough review of scientific articles published in a variety of databases, including Elsevier, Wiley, Web of Science, Springer, PubMed, Taylor and Francis, and Google Scholar. Furthermore, PhD and MSc theses were used in compiling and evaluating data obtained. Results: The ethnopharmacological applications of Pennisetum genus plants in various countries were established through detailed analysis of the aforementioned databases and thesis. So far, only a few species' chemical compositions and a total of 35 metabolites (excluding amino acids and fatty acid constituents) have been studied, including saponins, tannins, flavonoids, alkaloids, steroids, anthocyanin phenols, terpenoids, and others. The crude extracts were found to have antioxidant, antimicrobial, anti-cytotoxic, anti-hypertensive, and anti-inflammatory properties. Furthermore, the significance of ethnopharmacological applications, application, and the positive potential of Pennisetum species for the management of a variety of disorders was thoroughly examined. Conclusions: Although there are significant gaps in comprehending the traditional applications in the current available data, Pennisetum spp. are known to be rich in flavonoids, phenols, fatty acids, and amino acids with favorable medicinal characteristics. However, more research into the chemical makeup of innovative plant-derived medications is still needed. Furthermore, high-quality preclinical studies using a unique strategy are needed to assess the efficacy, safety, and mechanism of these plants.

Ethnopharmacological Relevance: The management of diabetes over the years has involved the use of herbal plants, which are now attracting interest. We assessed the antidiabetic properties of aqueous extract of C. purpureus shoots (AECPS) and the mechanism of action on pancreatic ß-cell dysfunction.Methods: This study was conducted using Thirty-six 36) male Wistar rats. The animals were divided into six equal groups (n = 6) and treatment was performed over 14 days. To induce diabetes in the rats, a single dose of 65 mg/kg body weight of alloxan was administered intraperitoneal along with 5% glucose. HPLC analysis was carried out to identified potential compounds in the extract. In vitro tests α-amylase, and α-glucosidase were analyzed. Body weight and fasting blood glucose (FBG) were measured. Biochemical parameters, such as serum insulin, liver glycogen, hexokinase, glucose-6-phosphate (G6P), fructose-1,6-bisphosphatase (F-1,6-BP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-ĸB), were analyzed. Additionally, mRNA expressions of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), B-cell lymphoma 2 (Bcl-2), and proliferating cell nuclear antigen (PCNA) were each evaluated.Results: This in vitro study showed inhibitory potency of Cenchrus purpureus extract (AECPS) as compared with the positive controls. AECPS showed a gradual decrease in alloxan-induced increases in FBG, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL-c), G6P, F-1,6-BP, malondialdehyde (MDA), IL-6, TNF-α, and NF-ĸB and increased alloxan-induced decreases in liver glycogen, hexokinase, and high density lipoprotein (HDL-c). The diabetic control group exhibited pancreatic dysfunction as evidenced by the reduction in serum insulin, homeostasis model assessment of ß-cell function (HOMA-β), expressions of PI3K/AKT, Bcl-2, and PCNA combined with an elevation in homeostatic model assessment of insulin resistance (HOMA-IR). High performance liquid chromatography (HPLC) revealed 3-O-rutinoside, ellagic acid, catechin, rutin, and kaempferol in AECPS.Conclusion: AECPS showed efficient ameliorative actions against alloxan-induced pancreatic dysfunction, oxidative stress suppression as well as, inflammation, and apoptosis via the activation of PI3K/AKT signaling pathways.

Vascularization is fundamental to the growth and spread of tumor cells to distant sites. As a consequence, angiogenesis, the sprouting of new blood vessels from existing ones, is a characteristic trait of cancer. In 1971, Judah Folkman postulated that tumour growth is angiogenesis dependent and that by cutting off blood supply, a neoplastic lesion could be potentially starved into remission. Decades of research have been devoted to understanding the role that vascular endothelial growth factor (VEGF) plays in tumor angiogenesis, and it has been identified as a significant pro-angiogenic factor that is frequently overexpressed within a tumor mass. Today, anti-VEGF drugs such as Sunitinib, Sorafenib, Axitinib, Tanibirumab, and Ramucirumab have been approved for the treatment of advanced and metastatic cancers. However, anti-angiogenic therapy has turned out to be more complex than originally thought. The failure of this therapeutic option calls for a reevaluation of VEGF as the major target in anti-angiogenic cancer therapy. The call for reassessment is based on two rationales: first, tumour blood vessels are abnormal, disorganized, and leaky; this not only prevents optimal drug delivery but it also promotes hypoxia and metastasis; secondly, tumour growth or regrowth might be blood vessel dependent and not angiogenesis dependent as tumour cells can acquire blood vessels via non-angiogenic mechanisms. Therefore, a critical assessment of VEGF, VEGFRs, and their inhibitors could glean newer options such as repurposing anti-VEGF drugs as vascular normalizing agents to enhance drug delivery of immune checkpoint inhibitors.

Objectives: The purpose of this study was to investigate the therapeutic activity of the cinnamic acid derivative KAD-3 (ethyl 3-(4-methoxyphenyl) acrylate) on Fe2+-induced oxidative hepatic damage via experimental and computer aided studies. Methods: Oxidative hepatic damage was induced via incubation of tissue supernatant with 0.1 mM FeSO4 for 30 min at 37 °C ex vivo with different concentration of KAD-3. Molecular docking, ADMET profiling, and density functional theory were conducted on the candidate to filter the properties of the drug candidate for drug design. Key findings: GSH, CAT, and ENTPDase activities were reduced when hepatic damage was induced (p

Type-2 diabetes mellitus (T2DM), is considered being a multifaceted disorder that presents a major therapeutic problem. Despite the widespread efforts in managing T2DM, drug discovery therapies remain insufficient. There are several new and vital antidiabetic drug agents under examination of many research clusters. Computational tools have influenced drug discovery at several levels. Hence, this study aimed to explain the molecular interactions via an in silico simulation approach between Aframomum melegueta seed-derived compounds as antidiabetic agents against carbohydrate metabolism regulatory target proteins (DPP-4, GSK-3, and GLP-1) involved in T2DM. Pharmacophore modeling, Auto-QSAR, induced-fit docking (IFD) simulation, free energy of binding affinity through the MM-GBSA method, and molecular docking were used to sort out the compounds as well as determining their drug ability. The results revealed the pharmacophore models created from the structures of DPP-4, GSK-3, and GLP-1 could determine the lead candidates with a restorative ability rate found near 100% of the actives in the comprehensive decoy database ranking. We predicted the pIC50 values of the compounds via a learning-based machine that was created by auto-QSAR. We authenticated the created model to confirm its analytical procedure. The greatest models attained for DPP-4, GSK-3, and GLP-1 were kpls_desc_35 (R2 = 0.73 and Q2 = 0.73), kpls_desc_4 (R2 = 0.72 and Q2 = 0.66), and kpls_radical_14 (R2 = 0.88 and Q2 = 0.64) and these confirmed models were used to predict the bioactivities of the hit candidates. While several isolated bioactive compounds from Aframomum melegueta revealed a better binding affinity score, binding free energy along with observance of RO5, only three compounds (ethinyl estradiol, 8-gingerol, and zingerone) revealed a more satisfactory pIC50. Thus, these compounds can be novel candidates for drug discovery in diabetes treatment.

Neurodegenerative diseases, for example Alzheimer’s, are perceived as driven by hereditary, cellular, and multifaceted biochemical actions. Numerous plant products, for example flavonoids, are documented in studies for having the ability to pass the blood-brain barrier and moderate the development of such illnesses. Computer-aided drug design (CADD) has achieved importance in the drug discovery world; innovative developments in the aspects of structure identification and characterization, bio-computational science, and molecular biology have added to the preparation of new medications towards these ailments. In this study we evaluated nine flavonoid compounds identified from three medicinal plants, namely T. diversifolia, B. sapida, and I. gabonensis for their inhibitory role on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoamine oxidase (MAO) activity, using pharmacophore modeling, auto-QSAR prediction, and molecular studies, in comparison with standard drugs. The results indicated that the pharmacophore models produced from structures of AChE, BChE and MAO could identify the active compounds, with a recuperation rate of the actives found near 100% in the complete ranked decoy database. Moreso, the robustness of the virtual screening method was accessed by well-established methods including enrichment factor (EF), receiver operating characteristic curve (ROC), Boltzmann-enhanced discrimination of receiver operating characteristic (BEDROC), and area under accumulation curve (AUAC). Most notably, the compounds’ pIC50 values were predicted by a machine learning-based model generated by the AutoQSAR algorithm. The generated model was validated to affirm its predictive model. The best models achieved for AChE, BChE and MAO were models kpls_radial_17 (R2 = 0.86 and Q2 = 0.73), pls_38 (R2 = 0.77 and Q2 = 0.72), kpls_desc_44 (R2 = 0.81 and Q2 = 0.81) and these externally validated models were utilized to predict the bioactivities of the lead compounds. The binding affinity results of the ligands against the three selected targets revealed that luteolin displayed the highest affinity score of −9.60 kcal/mol, closely followed by apigenin and ellagic acid with docking scores of −9.60 and −9.53 kcal/mol, respectively. The least binding affinity was attained by gallic acid (−6.30 kcal/mol). The docking scores of our standards were −10.40 and −7.93 kcal/mol for donepezil and galanthamine, respectively. The toxicity prediction revealed that none of the flavonoids presented toxicity and they all had good absorption parameters for the analyzed targets. Hence, these compounds can be considered as likely leads for drug improvement against the same.