Mitophagy and spermatogenesis: Role and mechanisms.

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.

In silico modeling revealed phytomolecules derived from Cymbopogon citratus (DC.) leaf extract as promising candidates for malaria therapy.

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.

Exploring redox imbalance and inflammation for asthma therapy.

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.

Beet leaf (beta vulgaris L.) extract attenuates iron-induced testicular toxicity: Experimental and computational approach.

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.

Apoptosis, inflammation, and oxidative stress in infertility: A mini review.

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.

Theobroma cacao fortified-feed ameliorates potassium bromate-induced oxidative damage in male Wistar rat.

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.

Plantain-based diet decreases oxidative stress and inflammatory markers in the testes of rats exposed to atrazine.

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.

Gallic acid abates cadmium chloride toxicity via alteration of neurotransmitters and modulation of inflammatory markers in Wistar rats.

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.

Therapeutic potential of rutin in male infertility: A mini review.

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.

Chemical fingerprinting, comparative in vitro antioxidant properties, and biochemical effects of ginger and bitterleaf infusion.

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.

Zingiber officinale and Vernonia amygdalina Infusions Improve Redox Status in Rat Brain.

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.

Biochemical evaluation and molecular docking assessment of Cymbopogon citratus as a natural source of acetylcholine esterase (AChE)- targeting insecticides.

Acetylcholinesterase (AChE) has been an effective target for insecticide development which is a very important aspect of the global fight against insect-borne diseases. The drastic reduction in the sensitivity of insects to AChE-targeting insecticides like organophosphates and carbamates have increased the need for insecticides of natural origin. In this study, we used Drosophila melanogaster as a model to investigate the insecticidal and AChE inhibitory potentials of Cymbopogon citratus and its bioactive compounds. Flies were exposed to 100 and 200 mg/mL C. citratus leaf extract for a 3-h survival assay followed by 45 min exposure for negative geotaxis and biochemical assays. Molecular docking analysis of 45 bioactive compounds of the plant was conducted against Drosophila melanogaster AChE (DmAChE). Exposure to C. citratus significantly reduced the survival rate of flies throughout the exposure period and this was accompanied by a significant decrease in percentage negative geotaxis, AChE activity, catalase activity, total thiol level and a significant increase in glutathione-S-transferase (GST) activity. The bioactive compounds of C. citratus showed varying levels of binding affinities for the enzyme. (+)-Cymbodiacetal scored highest (-9.407 kcal/mol) followed by proximadiol (-8.253 kcal/mol), geranylacetone (-8.177 kcal/mol), and rutin (-8.148 kcal/mol). The four compounds occupied the same binding pocket and interacted with important active site amino acid residues as the co-crystallized ligand (1qon). These compounds could be responsible for the insecticidal and AChE inhibitory potentials of C. citratus and they could be further explored in the development of AChE-targeting insecticides.

Hypoxia and the Kynurenine Pathway: Implications and Therapeutic Prospects in Alzheimer's Disease.

Neurodegenerative diseases (NDs) like Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, and Huntington's disease predominantly pose a significant socioeconomic burden. Characterized by progressive neural dysfunction coupled with motor or intellectual impairment, the pathogenesis of ND may result from contributions of certain environmental and molecular factors. One such condition is hypoxia, characterized by reduced organ/tissue exposure to oxygen. Reduced oxygen supply often occurs during the pathogenesis of ND and the aging process. Despite the well-established relationship between these two conditions (i.e., hypoxia and ND), the underlying molecular events or mechanisms connecting hypoxia to ND remain ill-defined. However, the relatedness may stem from the protective or deleterious effects of the transcription factor, hypoxia-inducible factor 1-alpha (HIF-1α). The upregulation of HIF-1α occurs in the pathogenesis of most NDs. The dual function of HIF-1α in acting as a "killer factor" or a "protective factor" depends on the prevailing local cellular condition. The kynurenine pathway is a metabolic pathway involved in the oxidative breakdown of tryptophan. It is essential in neurotransmission and immune function and, like hypoxia, associated with ND. Thus, a good understanding of factors, including hypoxia (i.e., the biochemical implication of HIF-1α) and kynurenine pathway activation in NDs, focusing on Alzheimer's disease could prove beneficial to new therapeutic approaches for this disease, thus the aim of this review.

Comparative effects of combined use of alcohol with cannabis and tobacco on testicular function in rats.

Alcoholism has been linked to problems with male reproductive function. The combined effects of alcohol, cannabis, and tobacco were compared in this study. A total of 35 rats were assigned randomly into seven groups A-G: animals in A were administered distilled water. Animals in B-G were either administered alcohol orally (30 ml 40% alcohol) or exposed to smoke from ignited tobacco (exposure to smoke from 0.7 g tobacco for 5 min) or cannabis (exposure to smoke from 0.7 g tobacco and cannabis for 5 min): B (orally administered alcohol), C (exposed to the smoke from tobacco), D (exposed to smoke from cannabis), E (treated with alcohol and exposed to smoke from tobacco), F (treated with alcohol and exposed to smoke from cannabis), G (treated with alcohol and exposed to smokes from tobacco and cannabis). Assays were carried on the testicular homogenate after a 14-day treatment. There was a significant increase in activity of alkaline phosphatase (P ≤ 0.05), concentrations of cholesterol, glutathione reductase, and malondialdehyde in treated rats by the co-administration of alcohol with cannabis and tobacco compared with the control group. The combined treatment also caused degeneration and morphological distortions of testicular cells. The biochemical and histoarchitectural change was due to oxidative damage attributable to the synergistic effects. The high binding energy of tetrahydrocannabinol ligand to prostate acid phosphatase may be a prediction that the ligand can have an inhibitory effect on the function of enzymes in the prostate.

Redox Homeostasis and Prospects for Therapeutic Targeting in Neurodegenerative Disorders.

Reactive species, such as those of oxygen, nitrogen, and sulfur, are considered part of normal cellular metabolism and play significant roles that can impact several signaling processes in ways that lead to either cellular sustenance, protection, or damage. Cellular redox processes involve a balance in the production of reactive species (RS) and their removal because redox imbalance may facilitate oxidative damage. Physiologically, redox homeostasis is essential for the maintenance of many cellular processes. RS may serve as signaling molecules or cause oxidative cellular damage depending on the delicate equilibrium between RS production and their efficient removal through the use of enzymatic or nonenzymatic cellular mechanisms. Moreover, accumulating evidence suggests that redox imbalance plays a significant role in the progression of several neurodegenerative diseases. For example, studies have shown that redox imbalance in the brain mediates neurodegeneration and alters normal cytoprotective responses to stress. Therefore, this review describes redox homeostasis in neurodegenerative diseases with a focus on Alzheimer's and Parkinson's disease. A clearer understanding of the redox-regulated processes in neurodegenerative disorders may afford opportunities for newer therapeutic strategies.