Leflunomide-induced cardiac injury in adult male mice and bioinformatic approach identifying Nrf2/NF-κb signaling interplay.

Leflunomide (LFND) is an immunosuppressive and immunomodulatory disease-modifying antirheumatic drug (DMARD) that was approved for treating rheumatoid arthritis. LFND-induced cardiotoxicity was not fully investigated since its approval. We investigated the cardiac injury in male mice and identified the role of nuclear factor erythroid 2-related factor 2/nuclear factor-κ B (Nrf2/NF-κB) signaling. Male albino mice were assigned into five groups as control, vehicle, and LFND (2.5, 5, and 10 mg/kg). We investigated cardiac enzymes, histopathology, and the mRNA expression of Nrf2, NF-κB, BAX, and tumor necrosis factor-α (TNF-α). The bioinformatic study identified the interaction between LFND and Nrf2/NF-κB signaling; this was confirmed by amelioration in mRNA expression (0.5- to 0.34-fold decrease in Nrf2 and 2.6- to 4.61-fold increases in NF-κB genes) and increased (1.76- and 2.625-fold) serum creatine kinase (CK) and 1.38- and 2.33-fold increases in creatine kinase-MB (CK-MB). Histopathological results confirmed the dose-dependent effects of LFND on cardiac muscle structure in the form of cytoplasmic, nuclear, and vascular changes in addition to increased collagen deposits and apoptosis which were increased compared to controls especially with LFND 10 mg/kg. The current study elicits the dose-dependent cardiac injury induced by LFND administration and highlights, for the first time, dysregulation in Nrf2/NF-κB signaling.

Role of ferroptosis pathways in neuroinflammation and neurological disorders: From pathogenesis to treatment.

Ferroptosis is a newly discovered non-apoptotic and iron-dependent type of cell death. Ferroptosis mainly takes place owing to the imbalance of anti-oxidation and oxidation in the body. It is regulated via a number of factors and pathways both inside and outside the cell. Ferroptosis is closely linked with brain and various neurological disorders (NDs). In the human body, the brain contains the highest levels of polyunsaturated fatty acids, which are known as lipid peroxide precursors. In addition, there is also a connection of glutathione depletion and lipid peroxidation with NDs. There is growing evidence regarding the possible link between neuroinflammation and multiple NDs, such as Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, and stroke. Recent studies have demonstrated that disruptions of lipid reactive oxygen species (ROS), glutamate excitatory toxicity, iron homeostasis, and various other manifestations linked with ferroptosis can be identified in various neuroinflammation-mediated NDs. It has also been reported that damage-associated molecular pattern molecules including ROS are generated during the events of ferroptosis and can cause glial activation via activating neuroimmune pathways, which subsequently leads to the generation of various inflammatory factors that play a role in various NDs. This review summarizes the regulation pathways of ferroptosis, the link between ferroptosis as well as inflammation in NDs, and the potential of a range of therapeutic agents that can be used to target ferroptosis and inflammation in the treatment of neurological disorders.

Design and Optimization of Omeprazole-Curcumin-Loaded Hydrogel Beads Coated with Chitosan for Treating Peptic Ulcers.

This study aimed to formulate a pharmaceutical dosage form containing omeprazole (OMP) and curcumin (CURC) to treat experimental peptic ulcers. OMP and CURC were preliminarily complexed with hydroxypropyl-ß-cyclodextrin for enhancing their solubilization. After that, the combined complex (CURC/OMP) was loaded to alginate beads to sustain their release and then coated with chitosan. Finally, we tested the anti-ulcerogenic impact of the best formula versus free OMP or OMP-only-loaded beads. The formulated spherical beads' diameter ranged from a minimum value of 1.5 ± 0.08 mm to 2.6 ± 0.24 mm; the swelling results ranged from 400.00 ± 8.5% to 800.00 ± 6.2%. The entrapment efficiency was in a range from 60.85 ± 1.01% to 87.44 ± 1.88%. The optimized formula (F8) showed a maximum EE% (87.44 ± 1.88%), swelling (800.00 ± 6.2%), and diameter in the range of 2.60 ± 0.24, with a desirability of 0.941. In the first hour following the administration of the free drug complex, 95% of OMP and 98% of CURC were released. This is unacceptable for medications that require a delayed release in the stomach. The initial drug release from hydrogel beads was 23.19% for CURC and 17.19% for OMP after 2 h and 73.09% for CURC and 58.26% for OMP after 12 h; however, after 24 h, 87.81% of CURC and 81.67% of OMP had been released. The OMP/CURC beads showed a more stable particle size (0.52 ± 0.01 mm) after 6 weeks. In conclusion, the OMP/CURC hydrogel beads give stronger anti-ulcer effectiveness compared to free OMP, CURC-only beads, and OMP-only-loaded beads, indicating a prospective application for managing peptic ulcers.

Elucidating the Potential Inhibitor against Type 2 Diabetes Mellitus Associated Gene of GLUT4.

Diabetes is a chronic hyperglycemic disorder that leads to a group of metabolic diseases. This condition of chronic hyperglycemia is caused by abnormal insulin levels. The impact of hyperglycemia on the human vascular tree is the leading cause of disease and death in type 1 and type 2 diabetes. People with type 2 diabetes mellitus (T2DM) have abnormal secretion as well as the action of insulin. Type 2 (non-insulin-dependent) diabetes is caused by a combination of genetic factors associated with decreased insulin production, insulin resistance, and environmental conditions. These conditions include overeating, lack of exercise, obesity, and aging. Glucose transport limits the rate of dietary glucose used by fat and muscle. The glucose transporter GLUT4 is kept intracellular and sorted dynamically, and GLUT4 translocation or insulin-regulated vesicular traffic distributes it to the plasma membrane. Different chemical compounds have antidiabetic properties. The complexity, metabolism, digestion, and interaction of these chemical compounds make it difficult to understand and apply them to reduce chronic inflammation and thus prevent chronic disease. In this study, we have applied a virtual screening approach to screen the most suitable and drug-able chemical compounds to be used as potential drug targets against T2DM. We have found that out of 5000 chemical compounds that we have analyzed, only two are known to be more effective as per our experiments based upon molecular docking studies and virtual screening through Lipinski's rule and ADMET properties.

Antidepressant and Anxiolytic Potentials of the Chewing Stick, Salvadora persica.

Materials and Methods: Salvadora persica stem bark was extracted with two different solvents, i.e., ethyl acetate and water, and preliminary phytochemical screening was performed. Two behavioral models were used: an elevated plus maze test (EPM) and the light and dark model test for anxiolytic parameters, and a forced swim test (FST) for antidepressant effects. Healthy mice weighing 18-40 gms were treated orally in four groups (n = 6), i.e., negative control treated with normal saline and positive control with 1 mg/kg diazepam (EPM) and 30 mg/kg fluoxetine (FST), and the test groups were treated with 500 mg/kg of aqueous and ethyl acetate Sp extract. The number of entries and duration spent in the open arm for 5 minutes were the parameters for evaluating the anxiolytic activity (EPM). Duration of immobility was measured for 5 min in the FST model. Results: In EPM, both the Sp extracts significantly (p < 0.005) increased the number of entries and the time spent in the open arms and was much similar to those of diazepam. Similarly, these extracts and fluoxetine significantly (p < 0.005) decreased the immobility time in FST. Conclusion: The results suggest the therapeutic potential of Salvadora persica an alternative in the management of comorbid anxiety and depression.

Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review.

Severe cases of COVID-19 are characterized by hyperinflammation induced by cytokine storm, ARDS leading to multiorgan failure and death. JAK-STAT signaling has been implicated in immunopathogenesis of COVID-19 infection under different stages such as viral entry, escaping innate immunity, replication, and subsequent inflammatory processes. Prompted by this fact and prior utilization as an immunomodulatory agent for several autoimmune, allergic, and inflammatory conditions, Jakinibs have been recognized as validated small molecules targeting the rapid release of proinflammatory cytokines, primarily IL-6, and GM-CSF. Various clinical trials are under investigation to evaluate Jakinibs as potential candidates for treating COVID-19. Till date, there is only one small molecule Jakinib known as baricitinib has received FDA-approval as a standalone immunomodulatory agent in treating critical COVID-19 patients. Though various meta-analyses have confirmed and validated the safety and efficacy of Jakinibs, further studies are required to understand the elaborated pathogenesis of COVID-19, duration of Jakinib treatment, and assess the combination therapeutic strategies. In this review, we highlighted JAK-STAT signalling in the pathogenesis of COVID-19 and clinically approved Jakinibs. Moreover, this review described substantially the promising use of Jakinibs and discussed their limitations in the context of COVID-19 therapy. Hence, this review article provides a concise, yet significant insight into the therapeutic implications of Jakinibs as potential anti-COVID agents which opens up a new horizon in the treatment of COVID-19, effectively.

An updated overview of cyanidins for chemoprevention and cancer therapy.

Anthocyanins are colored polyphenolic compounds that belong to the flavonoids family and are largely present in many vegetables and fruits. They have been used in traditional medicine in many cultures for a long time. The most common and abundant anthocyanins are those presenting an O-glycosylation at C-3 (C ring) of the flavonoid skeleton to form -O-ß-glucoside derivatives. The present comprehensive review summarized recent data on the anticancer properties of cyanidings along with natural sources, phytochemical data, traditional medical applications, molecular mechanisms and recent nanostrategies to increase the bioavailability and anticancer effects of cyanidins. For this analysis, in vitro, in vivo and clinical studies published up to the year 2022 were sourced from scientific databases and search engines such as PubMed/Medline, Google scholar, Web of Science, Scopus, Wiley and TRIP database. Cyanidins' antitumor properties are exerted during different stages of carcinogenesis and are based on a wide variety of biological activities. The data gathered and discussed in this review allows for affirming that cyanidins have relevant anticancer activity in vitro, in vivo and clinical studies. Future research should focus on studies that bring new data on improving the bioavailability of anthocyanins and on conducting detailed translational pharmacological studies to accurately establish the effective anticancer dose in humans as well as the correct route of administration.

Zinc finger protein­like 1 is a novel neuroendocrine biomarker for prostate cancer.

Prostate­derived calcitonin (CT) and its receptor induce tumorigenicity and increase metastatic potential of prostate cancer (PC). CT­inducible genes in human prostate were identified by subtraction hybridization. Among these genes, zinc finger protein like 1 (ZFPL1) protein was interesting since it was abundantly expressed in malignant prostates but was almost absent in benign prostates. ZFPL1 expression was upregulated by CT and androgens, and ZFPL1 protein was secreted by prostate tumor cells through exosomal secretion. Serum levels of ZFPL1 in cancer patients were at least 4­fold higher than those in the sera of cancer­free individuals. Cell biology of ZFPL1 suggests its localization in Golgi bodies and exosomes, and its colocalization with chromogranin A and CD44. These results suggested that ZFPL1 is secreted by tumor cells of neuroendocrine (NE)/stem cell phenotype. The knockdown of endogenous ZFPL1 in (PC) cells led to a remarkable decrease in cell proliferation, and invasion while increasing their apoptosis. As expected, the overexpression of ZFPL1 in prostate cells had an opposite effect on these functions. The knockdown of ZFPL1 in PC cells also decreased Akt phosphorylation, suggesting the actions of ZFPL1 may be mediated through the PI3K­Akt pathway. Moreover, the present results revealed that ZFPL1 is released by tumors cells of NE or androgen­independent phenotype and its serum levels are significantly higher in cancer patients, suggesting that it may serve as a blood­based non­invasive biomarker of aggressive PC.

Attitudes and knowledge about contraceptive use of saudi married women: a cross-sectional study approach

The speedy change in the Saudi Arabian community's socio-demographic pattern will significantly influence reproductive attitudes and practices with increasing preferences toward family planning because of the use of contraceptives. The current study was conducted to determine the attitudes and knowledge of married women in the Aseer region of Saudi Arabia regarding contraceptives use. Saudi married women from the Aseer region were the participants of this cross-sectional study. The study's objectives were covered via a standardized questionnaire, and the study comprised of 412 married women. A 100 % participant's response was demonstrated, while 31.8 % of the respondents were 31-40 years old. Most of the participants have a great awareness and knowledge about contraceptives, while (n=324; 78.6%) had previously used contraceptives. Additionally, 297 (72.1%) have intention to use contraceptive methods in the future. Majority of the participants (n=297; 91.6%) considered the economic and family planning as a reason for using the contraceptives, while natural family planning was mostly preferred (n=202; 49%). Logistic regression analysis exhibited significant correlation between the age, education, employment, monthly income and children number. The findings show that Saudi married women have high perceptions and knowledge of contraception. However, more effort is required to raise awareness regarding family planning and contraceptives, whereas the policy makers must exclude the obstacles to women from using contraceptives.

Medicinal Plants of Solanum Species: The Promising Sources of Phyto-Insecticidal Compounds.

Several medicinal plants have the potential to be a promising alternative pharmacological therapy for a variety of human illnesses. Many insects, including mosquitoes, are important vectors of deadly pathogens and parasites, which in the world's growing human and animal populations can cause serious epidemics and pandemics. Medicinal plants continue to provide a large library of phytochemicals, which can be used to replace chemically synthesized insecticides, and utilization of herbal product-based insecticides is one of the best and safest alternatives for mosquito control. Identifying new effective phyto-derived insecticides is important to counter increasing insect resistance to synthetic compounds and provide a safer environment. Solanum genus (Solanaceae family or nightshades) comprises more than 2500 species, which are widely used as food and traditional medicine. All research publications on insecticidal properties of Solanaceae plants and their phytoconstituents against mosquitoes and other insects published up to July 2020 were systematically analyzed through PubMed/MEDLINE, Scopus, EBSCO, Europe PMC, and Google Scholar databases, with focus on species containing active phytoconstituents that are biodegradable and environmentally safe. The current state of knowledge on larvicidal plants of Solanum species, type of extracts, target insect species, type of effects, name of inhibiting bioactive compounds, and their lethal doses (LC50 and LC90) were reviewed in this study. These studies provide valuable information about the activity of various species of Solanum and their phytochemical diversity, as well as a roadmap for optimizing select compounds for botanical repellents against a variety of vectors that cause debilitating and life-threatening human diseases.

Exploring the role of astrocytic dysfunction and AQP4 in depression.

Aquaporin-4 (AQP4) is the water regulating channel found in the terminal processes of astrocytes in the brain and is implicated in regulating the astrocyte functions, whereas in neuropathologies, AQP4 performs an important role in astrocytosis and release of proinflammatory cytokines. However, several findings have revealed the modulation of the AQP4 water channel in the etiopathogenesis of various neuropsychiatric diseases. In the current article, we have summarized the recent studies and highlighted the implication of astrocytic dysfunction and AQP4 in the etiopathogenesis of depressive disorder. Most of the studies have measured the AQP4 gene or protein expression in the brain regions, particularly the locus coeruleus, choroid plexus, prefrontal cortex, and hippocampus, and found that in these brain regions, AQP4 gene expression decreased on exposure to chronic mild stress. Few studies also measured the peripheral AQP4 mRNA expression in the blood and AQP4 autoantibodies in the blood serum and revealed no change in the depressed patients in comparison with normal individuals.

A Therapeutic Journey of Pyridine-based Heterocyclic Compounds as Potent Anticancer Agents: A Review (From 2017 to 2021).

Pyridine derivatives are the most common and significant heterocyclic compounds, which show their fundamental characteristics to various pharmaceutical agents and natural products. Pyridine derivatives possess several pharmacological properties and a broad degree of structural diversity that is most valuable for exploring novel therapeutic agents. These compounds have an extensive range of biological activities such as antifungal, antibacterial, anticancer, anti-obesity, anti-inflammatory, antitubercular, antihypertensive, antineuropathic, antihistaminic, antiviral activities, and antiparasitic. The potent therapeutic properties of pyridine derivatives allow medicinal chemists to synthesize novel and effective chemotherapeutic agents. Consequently, the imperative objective of this comprehensive review is to summarize and investigate the literature regarding recent advancements in pyridine-based heterocycles to treat several kinds of cancer. Furthermore, the performances of pyridine derivatives were compared with some standard drugs, including etoposide, sorafenib, cisplatin, and triclosan, against different cancer cell lines. We hope this study will support the new thoughts to pursue the most active and less toxic rational designs.

Verapamil attenuates oxidative stress and inflammatory responses in cigarette smoke (CS)-induced murine models of acute lung injury and CSE-stimulated RAW 264.7 macrophages via inhibiting the NF-κB pathway.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), severe form of ALI, are characterized by overwhelming of lung inflammation, and no treatment is currently available to treat ALI/ARDS. Cigarette smoke (CS) is one of the prime causes to induce ALI/ARDS via oxidative stress. Despite extensive research, no appropriate therapy is currently available to treat ALI/ARDS. Hence, new potential approaches are needed to treat ALI/ARDS. Consequently, this project was designed to explore the protective effects of verapamil against CS-induced ALI by in vivo and in vitro method. In vivo data obtained from respiratory mechanics, pulmonary morphometric analyses and lung histopathology revealed that verapamil dose-dependently and strikingly decreased the lung weight coefficient, attenuated the albumin exudation into lungs, minimized the infiltration of macrophages and neutrophils into lungs, reduced the pro-inflammatory cytokines (tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and keratinocyte chemoattractant (KC)) production, and improved the hypoxemia and lung histopathological changes. Similarly, verapamil also reduced the production of TNF-α, IL-6 and KC from cigarette smoke extract (CSE)-stimulated RAW 264.7 macrophage. Importantly, verapamil dose-dependently and remarkably suppressed the CS-induced oxidative stress via not only reducing the myeloperoxidase (MPO) activity of lungs, total oxidative stress (TOS) and malondialdehyde (MDA) content in the lungs and supernatant of RAW 264.7 macrophage but also improving total antioxidant capacity (TAC) and superoxide dismutase (SOD) production. Finally, verapamil strikingly decreased the NF-κB expression both in in vivo and in vitro models. Hence, verapamil has positive therapeutic effects against CS-induced ALI via suppressing uncontrolled inflammatory response, oxidative stress and NF-κB p65 signaling.

Hormonal Therapy for Gynecological Cancers: How Far Has Science Progressed toward Clinical Applications?

In recent years, hormone therapy has been shown to be a remarkable treatment option for cancer. Hormone treatment for gynecological cancers involves the use of medications that reduce the level of hormones or inhibit their biological activity, thereby stopping or slowing cancer growth. Hormone treatment works by preventing hormones from causing cancer cells to multiply. Aromatase inhibitors, anti-estrogens, progestin, estrogen receptor (ER) antagonists, GnRH agonists, and progestogen are effectively used as therapeutics for vulvar cancer, cervical cancer, vaginal cancer, uterine cancer, and ovarian cancer. Hormone replacement therapy has a high success rate. In particular, progestogen and estrogen replacement are associated with a decreased incidence of gynecological cancers in women infected with human papillomavirus (HPV). The activation of estrogen via the transcriptional functionality of ERα may either be promoted or decreased by gene products of HPV. Hormonal treatment is frequently administered to patients with hormone-sensitive recurring or metastatic gynecologic malignancies, although response rates and therapeutic outcomes are inconsistent. Therefore, this review outlines the use of hormonal therapy for gynecological cancers and identifies the current knowledge gaps.

Synthesis and Photoluminescence Properties of MoS2/Graphene Heterostructure by Liquid-Phase Exfoliation.

Here, we report the synthesis of MoS2/graphene heterostructure in single-stage, liquid-phase exfoliation using a 7:3 isopropyl alcohol/water mixture. Further, the synthesized heterostructure was characterized using UV-visible and micro-Raman spectroscopies, transmission electron microscopy (TEM), and dynamic light scattering (DLS) analysis. UV-visible and micro-Raman analyses confirmed that the synthesized heterostructure had mostly few-layered (two-to-four sheets) MoS2. The photophysical properties of the heterostructure were analyzed using steady-state and time-resolved luminescence techniques. Enhanced photoluminescence was observed in the case of the heterostructure probably due to an increase in the defect sites or reduction in the rate of nonradiative decay upon formation of the sandwiched heterostructure. Applications of this heterostructure for fluorescence live-cell imaging were carried out, and the heterostructure demonstrated a better luminescence contrast compared to its individual counterpart MoS2 in phosphate-buffered saline (PBS).

Computational screening and biochemical analysis of Pistacia integerrima and Pandanus odorifer plants to find effective inhibitors against Receptor-Binding domain (RBD) of the spike protein of SARS-Cov-2.

Although World Health Organization-approved emergency vaccines are available in many countries, the mortality rate from COVID-19 remains high due to the fourth or fifth wave and the delta variant of the coronavirus. Thus, an effective mechanistic investigation in treating this disease is urgently needed. In this work, we extracted phytochemicals from two mangrove plants, Pistacia integerrima and Pandanus odorifer, assessing their potential actions against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2. The antioxidant activities of Pistacia integerrima leaves and fruits were 142.10 and 97.13 µg/mL, respectively, whereas Pandanus odorifer leaves and fruits were 112.50 and 292.71 µg/mL, respectively. Furthermore, leaf extracts from both plants had lower cytotoxicity against Artemia salina than fruit extracts. Gas chromatography-mass spectrometry analysis revealed a total of 145 potential phytochemicals from these extracts. Three phytochemicals, 28-demethyl-beta-amyrone, 24-Noroleana-3,12-diene, and stigmasterol, displayed binding free energy values of - 8.3, -7.5, and - 8.1 Kcal/mol, respectively, in complexes with the spike protein of SARS-CoV-2. The root-mean-square deviation, solvent-accessible surface area, radius of gyration, root-mean-square fluctuations, and hydrogen bonds were used to ensure the binding stability of the docked complexes in the atomistic simulation. Thus, wet-lab validations are necessary to support these findings.

Alleviation of neuropathic pain by trazodone in rats

Abstract Neuropathic pain is generally characterised by an abnormal sensation (dysesthesia), an increased response to painful stimuli (hyperalgesia), and pain in response to a stimulus that does not normally provoke pain (allodynia). The present study was designed to investigate the effect of trazodone (5mg/kg and 10mg/kg) on peripheral neuropathic pain induced by partial sciatic nerve ligation in rats. Mechanical hyperalgesia, cold allodynia and thermal hyperalgesia were assessed by performing the pinprick, acetone, and hot plate tests, respectively. Biochemically, lipid peroxidation level and total calcium levels were measured. However, trazodone administration (5 and 10 mg/ kg i.p.) for 21days significantly diminished partial sciatic nerve ligation-induced neuropathic pain along with areduction in oxidative stress and calcium levels. The results of the present study suggest that trazodone is effective in attenuating partial sciatic nerve ligation-inducedpainful neuropathic states, which may be attributed to decreased oxidative stress and calcium levels.

LC-MS/HRMS Analysis, Anti-Cancer, Anti-Enzymatic and Anti-Oxidant Effects of Boerhavia diffusa Extracts: A Potential Raw Material for Functional Applications.

Boerhavia diffusa is a great tropical plant and is widely used for various traditional purposes. In the present study, we examined the influence of solvents (dichloromethane, ethyl acetate, methanol and infusion (water)) on chemical composition and biological capabilities of B. diffusa. An UHPLC-HRMS method was used to determine the chemical characterization. The biological ability was examined for antioxidant, enzyme inhibitory and anti-cancer effects. To evaluate antioxidant effects, different chemical methods (ABTS, DPPH, CUPRAC, FRAP, metal chelating and phosphomolybdenum) were applied. With regard to enzyme inhibitory properties, cholinesterases, amylase, glucosidase and tyrosinase were used. The MDA-MB-231 breast cancer cell line was chosen to determine anticancer activity. Based on the UHPLC-HRMS analysis, 37 specialized metabolites were dereplicated and identified in the studied extracts. Results revealed the presence of 15 hydroxybenzoic, hydroxycinnamic, acylquinic acids, and their glycosides, one rotenoid, seven flavonoids, 12 fatty acids and two other glycosides. Among the tested extracts, the methanol extract showed a stronger antioxidant ability compared with other extracts. The methanol extract also showed the best inhibitory effects on tyrosinase and glucosidase. In the anti-cancer evaluation, the methanol extract showed stronger anticancer effects compared with water extract. In summary, our observations can contribute to the establishment of B. diffusa as a potential candidate for functional applications in the preparation.

Analysis of Codon Usage of Speech Gene FoxP2 among Animals.

The protein-coding gene FoxP2 (fork head box protein P2) plays a major role in communication and evolutionary changes. The present study carried out a comprehensive codon usage bias analysis in the FoxP2 gene among a diverse group of animals including fishes, birds, reptiles, and mammals. We observed that in the genome of fishes for the FoxP2 gene, codons ending with C or G were most frequently used, while in birds, reptiles, and mammals, codons ending with T or A were most frequently used. A higher ENC value was observed for the FoxP2 gene indicating a lower CUB. Parity role two-bias plots suggested that apart from mutation pressure, other factors such as natural selection might have influenced the CUB. The frequency distribution of the ENC observed and ENC expected ratio revealed that mutation pressure plays a key role in the patterns of codon usage of FoxP2. Besides, correspondence analysis exposed the composition of the nucleobase under mutation bias affects the codon usage of the FoxP2 gene. However, neutrality plots revealed the major role of natural selection over mutation pressure in the CUB of FoxP2. In addition, the codon usage patterns for FoxP2 among the selected genomes suggested that nature has favored nearly all the synonymous codons for encoding the corresponding amino acid. The uniform usage of 12 synonymous codons for FoxP2 was observed among the species of birds. The amino acid usage frequency for FoxP2 revealed that the amino acids Leucine, Glutamine, and Serine were predominant over other amino acids among all the species of fishes, birds, reptiles, and mammals.