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Research into the impacts of oxidative stress (OS), and hormonal balance on reproductive potential has increased over the last 40 years possibly due to rising male infertility. Decreased antioxidant levels and increased OS in tissues result from hormonal imbalance, which in turn leads to male infertility. Increased reactive oxygen species (ROS) generation in seminal plasma has been linked to many lifestyle factors such as alcohol and tobacco use, toxicant exposure, obesity, varicocele, stress, and aging. This article provides an overview of the crosslink between OS and gonadal hormone disruption, as well as a potential mode of action in male infertility. Disrupting the equilibrium between ROS generation and the antioxidant defense mechanism in the male reproductive system may affect key hormonal regulators of male reproductive activities. Unchecked ROS production may cause direct injury on reproductive tissues or could disrupt normal regulatory mechanisms of the hypothalamic-pituitary-gonadal (HPG) axis and its interaction with other endocrine axes, both of which have negative effects on male reproductive health and can lead to male infertility.

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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.

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The present study evaluated the effects of ginger and bitterleaf tea infusions on redox and inflammatory balance in rats. Twenty-four Wistar rats with weights of between 160 and 180 g were assigned into four (4) groups (n = 6). The control group received distilled water, while the remaining groups were administered tea infusions of ginger, bitterleaf, or a combination of both at 5 mg/mL, respectively. Bitterleaf and ginger teas elevated the levels of superoxide dismutase, catalase, glutathione peroxidase, and reduced glutathione in rat plasma and liver, while malondialdehyde levels decreased. Furthermore, ginger tea caused an increase in the expression of nuclear factor erythroid-2-related factor 2 (Nrf-2) and reduced tumor necrosis factor alpha (TNF-α). The GC-MS analysis of the teas identified 77 chemical compounds, among which gingerol and precocene I were predominant. Collectively, the findings indicate, in particular, that ginger tea may boost antioxidant and anti-inflammatory capacity by increasing Nrf-2 levels.

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In recent decades, there has been a substantial decline in sperm quality in humans, with lifestyle factors playing a major role in this trend. There are several lifestyle factors which are contributing to male infertility. This review, however, discusses factors such as obesity, diet/nutrition, psychological stress, radiation exposure, cigarette smoking, and alcohol use with reference to male infertility. Sperm count, motility, morphology and sperm DNA may be adversely affected by lifestyle factors, which may also affect the endocrine regulation of reproductive function. The decline in male fertility has a significant impact on fertility rates, and the resulting implications for the human population make this a serious public health concern in the twenty-first century. Thus, lifestyle interventions through a specific framework of educational, environmental, nutritional/physical exercise, and psychological support coupled with the use of nutritional antioxidants supplements can help couples achieve better health and well-being and improve their fertility prospects or increase their chances of conception.

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Exposure to the herbicide atrazine has been shown to have deleterious effects on human and animal reproduction. To determine whether atrazine influences the brain-pituitary-testicular axis directly or indirectly, the present study examined the toxic effects of atrazine on fertility potential by assessing gonadal hormones, testicular function indices, sperm quality, and oxido-inflammatory markers in rats. Twelve animals were grouped into two groups; control and atrazine. The control group received oral administration of olive oil (2 mL/kg), while the atrazine group received 120 mg/kg of atrazine. Treatments were daily and lasted for 7 days. Upon treatment cessation, rats were necropsied for biochemical and histopathological analyses. The biochemical function indices in the rat brain, testis, and epididymis decreased significantly in the atrazine group. Atrazine exposure led to decreases in gonadal hormonal concentrations, semen quality parameters, and testicular function indices compared with the control. Furthermore, there was a marked increase in oxidative stress and inflammatory markers as well as degeneration of the histo-architecture in atrazine-treated rats. Overall, atrazine exposure impaired sperm quality, led to increased inflammation and oxidative stress, and decreased the activity of the brain-pituitary-testicular axis via endocrine disruption.

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The emergence of varying levels of resistance to currently available antimalarial drugs significantly threatens global health. This factor heightens the urgency to explore bioactive compounds from natural products with a view to discovering and developing newer antimalarial drugs with novel mode of actions. Therefore, we evaluated the inhibitory effects of sixteen phytocompounds from Cymbopogon citratus leaf extract against Plasmodium falciparum drug targets such as P. falciparum circumsporozoite protein (PfCSP), P. falciparum merozoite surface protein 1 (PfMSP1) and P. falciparum erythrocyte membrane protein 1 (PfEMP1). In silico approaches including molecular docking, pharmacophore modeling and 3D-QSAR were adopted to analyze the inhibitory activity of the compounds under consideration. The molecular docking results indicated that a compound swertiajaponin from C. citratus exhibited a higher binding affinity (-7.8 kcal/mol) to PfMSP1 as against the standard artesunate-amodiaquine (-6.6 kcal/mol). Swertiajaponin also formed strong hydrogen bond interactions with LYS29, CYS30, TYR34, ASN52, GLY55 and CYS28 amino acid residues. In addition, quercetin another compound from C. citratus exhibited significant binding energies -6.8 and -8.3 kcal/mol with PfCSP and PfEMP1, respectively but slightly lower than the standard artemether-lumefantrine with binding energies of -7.4 kcal/mol against PfCSP and -8.7 kcal/mol against PfEMP1. Overall, the present study provides evidence that swertiajaponin and other phytomolecules from C. citratus have modulatory properties toward P. falciparum drug targets and thus may warrant further exploration in early drug discovery efforts against malaria. Furthermore, these findings lend credence to the folkloric use of C. citratus for malaria treatment.Communicated by Ramaswamy H. Sarma.

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Plants have been used in various regions of the world to treat various medical conditions including male infertility. The review aims to evaluate the pharmacological effects of watermelon consumption in improving male fertility and sexual function. Watermelon is a popular fruit consumed around the world for its diverse nutritional and health-promoting qualities. This study showed the mechanism via which watermelon enhances male fertility as it was reported for improving semen quality, reversing erectile dysfunction, enhancing testicular redox status, as well as improving gonadotropin secretion. These activities have been linked to their constituents as it contains vitamins and phytochemicals such as phenols and certain flavonoids that contribute to their antioxidant properties. Watermelon has also been noted to possess antimicrobial, anti-helminthic, antioxidant, antidiabetic, anti-inflammatory, and antihypertensive properties that may contribute to its therapeutic use.

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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 < 0.05) decreased the activities of GSH, SOD, CAT, and ENTPDase. In contrast, induction of testicular damage also resulted in a significant increase in MDA and NO levels and an increase in ATPase, G6Pase, and F-1,6-BPase activities. BVLE treatment (p < 0.05) reduced these levels and activities compared to control levels. An HPLC investigation revealed fifteen compounds in BVLE, with quercetin being the most abundant. The molecular docking and MDS analysis of the present study suggest that schaftoside may be an effective allosteric inhibitor of fructose 1,6-bisphosphatase based on the interacting residues and the subsequent effect on the dynamic loop conformation. These findings indicate that B. vulgaris can protect against Fe2+-induced testicular injury by suppressing oxidative stress, acetylcholinesterase, and purinergic activities while regulating carbohydrate dysmetabolism.

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BACKGROUND: Asthma is a prolonged inflammatory disorder of the airways, that affects an estimated 300 million people worldwide. Asthma is triggered by numerous endogenous and exogenous stimuli with symptoms like wheezing, cough, short of breath, chest tightening, airway obstruction, and hyperreactivity observed in patients. OBJECTIVE: The review seeks to identify targets of redox imbalance and inflammation that could be explored to create effective treatments for asthma. METHODS: The methodology involved a search and review of literature relating to asthma pathogenesis, redox homeostasis, and inflammation. RESULTS:  Eosinophils and neutrophils are involved in asthma pathogenesis. These inflammatory cells generate high levels of endogenous oxidants such as hydrogen peroxide and superoxide, which could result in redox imbalance in the airways of asthmatics. Redox imbalance occurs when the antioxidant systems becomes overwhelmed resulting in oxidative stress. Oxidative stress and inflammation have been linked with asthma inflammation and severity. Reactive oxygen species (ROS)/reactive nitrogen species (RNS) cause lung inflammation by activating nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK), activator protein-1, as well as additional transcription factors. These factors stimulate cytokine production which ultimately activates inflammatory cells in the bronchi, causing lung cellular injury and destruction. ROS/RNS is also produced by these inflammatory cells to eradicate invading bacteria. Antioxidant treatments for asthma have not yet been fully explored. CONCLUSION: Redox and inflammatory processes are viable targets that could be explored to create better therapy for asthma.

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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.

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Some therapeutic and beneficial health properties of the Theobroma cacao leaf have been documented. This study evaluated the ameliorative effect of Theobroma cacao-fortified feed against potassium bromate-induced oxidative damage in male Wistar rats. Thirty rats were randomly grouped into A-E. Except for E (the negative control), the rats in the other groups were administered 0.5 ml of 10 mg/kg body weight of potassium bromate daily using oral gavage and then allowed access to feed and water ad libitum. Groups B, C, and D were fed with 10 %, 20 %, and 30 % leaf-fortified feed respectively, while the negative and positive control (A) was fed with commercial feed. The treatment was carried out consecutively for fourteen days. In the liver and kidney, there was a significant increase (p < 0.05) in total protein concentration, a significant decrease (P < 0.05) in MDA level, and SOD activity in the fortified feed group compared to the positive control. Furthermore, in the serum, there was a significant increase (p < 0.05) in the albumin concentration, and ALT activity, and a significant decrease (p < 0.05) in urea concentration in the fortified feed groups compared to the positive control. The histopathology of the liver and kidney in the treated groups showed moderate cell degeneration compared to the positive control group. Antioxidant activity due to the presence of flavonoids and metal chelating activity of fiber in Theobroma cacao leaf could be responsible for the ameliorative effect of the fortified feed against potassium bromate-induced oxidative damage.

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Male infertility has become a problem worldwide, and recent research has emphasized the development of more effective therapy options. Among natural compounds, rutin has been widely studied for its potential to treat dysfunction related to male infertility, including a reduction in sperm quality, spermatogenesis disruption and structural disruption in the testis. A thorough review of scientific literature published in several databases, including Google Scholar, PubMed/MEDLINE and Scopus, was used to synthesize the present state of research on the role of rutin in male reproductive health. Rutin has been shown to possess antiapoptotic, antioxidant and anti-inflammatory activities, among others, which are crucial in the management of male infertility. Numerous investigations have shown that rutin protects against male infertility and have explored the underlying mechanisms involved. The present review, therefore, assesses the therapeutic mechanisms involved in male infertility treatment using rutin. Rutin was able to mitigate the induced oxidative stress, apoptosis, inflammation, and related physiological processes that can cause testicular dysfunction. Please cite this article as: Rotimi DE, Elebiyo TC, Ojo OA. Therapeutic potential of rutin in male infertility: A mini review. J Integr Med. 2023; 21(2): 130-135.

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Cadmium is a highly neurotoxic heavy metal that disrupts membranes and causes oxidative stress in the brain. The study aimed to investigate the neuroprotective effect of gallic acid on oxidative damage in the brains of Wistar rats exposed to cadmium chloride (CdCl2). Male Wistar rats were divided into four groups of five rats each. Group 1 was administered distilled water only throughout the study. Throughout the study, Group 2 received CdCl2 alone (5 mg/kg b.w./day), Group 3 received gallic acid (20 mg/kg b.w./day), and Group 4 received CdCl2 + gallic acid (20 mg/kg). Treatments were oral with distilled water as a vehicle. The study lasted 21 days. In the brain, the activities of cholinesterase and antioxidant enzymes were evaluated, as well as the levels of reduced glutathione, malondialdehyde, neurotransmitters, Na+/K+ ATPase, myeloperoxidase activity, nitric oxide, and interleukin-6. CdCl2-induced brain impairments in experimental animals and gallic acid prevents the following CdCl2-induced activities: inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), elevated neurotransmitters (serotonin and dopamine), decreased antioxidant enzymes (superoxide dismutase, catalase), decreased glutathione, Na+/K+ ATPases, and increased MDA and neuroinflammatory markers (myeloperoxidase (MPO), nitric oxide, and interleukin-6 in the brain of experimental rats exposed to CdCl2 (p < 0.05). Taken together, the neuroprotective effects of gallic acid on CdCl2-induced toxicity in the brains of rats suggest its potent antioxidant and neurotherapeutic properties.

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Exposure to the herbicide atrazine (ATZ) has deleterious effects on male fertility. This fact underscores the need for measures to protect against the detrimental impact of atrazine exposure on male fertility. The study assessed the protective effects of plantain-based diet (PBD) on rat testes exposed to ATZ by exploring oxid-inflammatory homeostasis. The study evaluated the preventive and therapeutic effects of PBD in a two-phased experiment. Male rats were randomized into seven groups for therapeutic model (Control, ATZ only, ATZ recovery, ATZ + 50% PBD, ATZ + 25% PBD, ATZ + 12.5% PBD and ATZ + quercetin-QUE) while the preventive model had ten groups (Control, ATZ, 50% PBD + ATZ, 25% PBD + ATZ, 12.5% PBD + ATZ and QUE + ATZ). The oxidative stress parameters (DNA fragmentation and MDA level), purinergic activity (ATPase), acetylcholine esterase, and inflammatory markers (NO level, MPO activity, and TNF-α) were increased while the Nrf2 levels were decreased by the ATZ treatment. However, the PBD was able to restore the oxido-inflammatory parameters in the rat testes. The chemical fingerprint of the diet revealed that the diets contained 16 bioactive compounds with quercetin being the most prominent compound. Overall, treatment with PBD was able to protect and prevent the toxicity caused by ATZ by modulating the redox and inflammatory status as well as purinergic activity in the rat testes.

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Severe SARS-CoV-2 infection causes systemic inflammation, cytokine storm, and hypercytokinemia due to activation of the release of pro-inflammatory cytokines that have been associated with case-fatality rate. The immune overreaction and cytokine storm in the infection caused by SARS-CoV-2 may be linked to NLRP3 inflammasome activation which has supreme importance in human innate immune response mainly against viral infections. In SARS-CoV-2 infection, NLRP3 inflammasome activation results in the stimulation and synthesis of natural killer cells (NKs), NFκB, and interferon-gamma (INF-γ), while inhibiting IL-33 expression. Various efforts have identified selective inhibitors of NLRP3 inflammasome. To achieve this, studies are exploring the screening of natural compounds and/or repurposing of clinical drugs to identify potential NLRP3 inhibitors. NLRP3 inflammasome inhibitors are expected to suppress exaggerated immune reaction and cytokine storm-induced-organ damage in SARS-CoV-2 infection. Therefore, NLRP3 inflammasome inhibitors could mitigate the immune-overreaction and hypercytokinemia in Covid-19 infection.

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The study investigated the effects of Zingiber officinale root and Vernonia amygdalina leaf on the brain redox status of Wistar rats. Twenty-four (24) rats weighing 160 ± 20 g were randomly assigned into four (4) groups, each with six (6) rats. Animals in Group 1 (control) were orally administered distilled water (1 mL), while the test groups were orally administered 5 mg/mL of either Z. officinale, V. amygdalina infusion, or a combination of both, respectively, for 7 days. The rats were sacrificed at the end of treatments and blood and tissue were harvested and prepared for biochemical assays. Results showed that administration of V. amygdalina and Z. officinale, as well as their coadministration, reduced the levels of malondialdehyde (MDA), nitric oxide (NO), acetylcholinesterase (AChE), and myeloperoxidase (MPO) in rat brain tissue compared with the control group. Conversely, coadministration of V. amygdalina and Z. officinale increased the levels of reduced glutathione (GSH) in rat brain tissue compared with the control group. However, the administration of the infusions singly, as well as the combination of both infusions, did not have any effect on the rat brain levels of glutathione peroxidase (GPx) and catalase (CAT) antioxidant enzymes compared to the control. Taken together, the findings indicate that the V. amygdalina and Z. officinale tea infusions have favorable antioxidant properties in the rat brain. The findings are confirmatory and contribute to deepening our understanding of the health-promoting effects of V. amygdalina and Z. officinale tea infusions.

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Botanicals with remarkable pharmacological properties include Zingiber officinale Roscoe [Zingiberaceae] (ginger) and Gymnanthemum amygdalinum (Delie) Sch. Bip [Asteraceae] (bitterleaf). The plants are frequently used as teas and decoctions, and have been studied in the treatment of various illnesses. Thus, this study investigated the in vitro antioxidant activities and chemical fingerprints of ginger and bitter leaf infusions separately and as a combination. In addition, we assessed the effects of the tea infusions on rat liver and kidney indices. The findings from this study showed that the bitterleaf infusion had the highest phenolic content (21.77 ± 3.140 µg gallic acid equivalent/mg) in comparison with that of ginger (15.17 ± 1.50 µg gallic acid equivalent/mg) and their combination (8.81 ± 0.48 µg gallic acid equivalent/mg). The ginger infusion had the highest flavonoid content (547.15 ± 1.17 µg quercetin equivalent/mg), which was preceded by bitterleaf (473.02 ± 10.48 µg quercetin equivalent/mg) and the ginger and bitterleaf infusion (415.08 ± 4.15 µg quercetin equivalent/mg). Furthermore, our results showed that the tea infusions had no significant effect on the liver function indices (ALT and AST) compared to the control. In contrast, the rat plasma urea significantly increased in the groups given bitterleaf and a combination of ginger and bitterleaf infusions, while creatinine significantly decreased in the group that received the combined form of the infusion. The GC-MS analysis of ginger and bitterleaf infusions revealed that n-hexadecanoic acid, oleic acid, and ergosterol were most abundant in the bitterleaf infusion. At the same time, gingerol, 2-butanone, and 4-(4-hydroxy-3-methoxyphenyl) were the most abundant in the ginger infusion. Together, the findings are not only evidence in support of the medicinal value of these plants but also reinforce their prospects as nutriceuticals.

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Several processes including oxidative stress, apoptosis, inflammation and autophagy are related to testicular function. Recent studies indicate that a crosstalk between apoptosis and autophagy is essential in regulating testicular function. Autophagy and apoptosis communicate with each other in a complex way, allowing them to work for or against each other in testicular cell survival and death. Several xenobiotics especially endocrine-disrupting chemicals (EDCs) have caused reproductive toxicity because of their potential to modify the rate of autophagy and trigger apoptosis. Therefore, the purpose of the present review was to shed light on how autophagy and apoptosis interact together in the testis.

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The current work investigated the chemical profile, antimalarial potential and capacity of hydroethanolic Senna alata extract (SAE) to reverse hematological and biochemical pertubation in Plasmodium berghei infected mice. Results of the phytochemical analysis revealed the presence of alkaloids, flavonoids, phenolics, tannins, terpenoids, saponins, steroids and cardiac glycosides. Total phenolic and flavonoid content was estimated to be 45.29 ± 2.34 mg GAE/g and 25.22 ± 2.26 mg QE/g respectively. In vitro analysis of the extract also confirmed its antioxidant property. Results of the test for prophylaxis of P. berghei indicated that SAE suppressed parasitemia significantly in treated groups in a dose dependent manner when compared with negative control group. Similarly, SAE improved the mean survival time (MST) and packed cell volume (PCV) of infected mice. The test for curative effect showed that SAE significantly suppressed parasitemia to 4.50 ± 1.05% compared to untreated group 29.83 ± 3.49%. Results of liver and kidney functions indices of treated animals indicated that whereas infection with P. berghei caused increase in the levels of AST, ALT, ALP, urea and creatinine, treatment with SAE significantly reversed the perturbation. Similarly, infected mice were dyslipidemic with concomitant increased activity of HMG CoA reductase and decreased activity of antioxidant enzymes with increase in lipid peroxides levels. However, these alterations were significantly reversed by administration of SAE. Results of this study shows that Senna alata possess antimalarial activity and therefore justify the traditional use of plant for the treatment of malaria.

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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.

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