Oxidative stress can affect the protein, lipids, and DNA of the cells and thus, play a crucial role in several pathophysiological conditions. It has already been established that oxidative stress has a close association with inflammation via nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway. Amino acids are notably the building block of proteins and constitute the major class of nitrogen-containing natural products of medicinal importance. They exhibit a broad spectrum of biological activities, including the ability to activate NRF2, a transcription factor that regulates endogenous antioxidant responses. Moreover, amino acids may act as synergistic antioxidants as part of our dietary supplementations. This has aroused research interest in the NRF2-inducing activity of amino acids. Interestingly, amino acids' activation of NRF2-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway exerts therapeutic effects in several diseases. Therefore, the present review will discuss the relationship between different amino acids and activation of NRF2–KEAP1 signaling pathway pinning their anti-inflammatory and antioxidant properties. We also discussed amino acids formulations and their applications as therapeutics. This will broaden the prospect of the therapeutic applications of amino acids in a myriad of inflammation and oxidative stress-related diseases. This will provide an insight for designing and developing new chemical entities as NRF2 activators.

Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) that causes COVID-19 infections penetrates body cells by binding to angiotensin-converting enzyme-2 (ACE2) receptors. Evidence shows that SARS-CoV-2 can also affect the urogenital tract. Hence, it should be given serious attention when treating COVID-19-infected male patients of reproductive age group. Other viruses like HIV, mumps, papilloma and Epstein–Barr can induce viral orchitis, germ cell apoptosis, inflammation and germ cell destruction with attending infertility and tumors. The blood-testis barrier (BTB) and blood-epididymis barrier (BEB) are essential physical barricades in the male reproductive tract located between the blood vessel and seminiferous tubules in the testes. Despite the significant role of these barriers in male reproductive function, studies have shown that a wide range of viruses can still penetrate the barriers and induce testicular dysfunctions. Therefore, this mini-review highlights the role of ACE2 receptors in promoting SARS-CoV-2-induced blood-testis/epididymal barrier infiltration and testicular dysfunction.

Male infertility caused by exposure to heavy metals is a current global issue. Exposure to cadmium chloride (CdCl2) negatively affects the male reproductive system. Many infertile people, especially in developing countries, resort to folkloric treatment. Plukenetia conophora is used in Nigerian folk medicine to promote fertility. This study investigated the effects of Plukenetia conophora (PC) and 4H-Pyran-4-One 2,3-Dihydro-3,5-Dihydroxy-6-Methyl (DDMP) on Wistar rats with cadmium chloride-induced testicular damage. Forty-two male Wistar rats (150-190g) were divided into seven groups (n=6) and treated daily for 54 days as follows: Controls (normal saline); CdCl2 (2mg/kg single IP dose); CdCl2 + 200 mg/kg vitamin E; CdCl2 + 100 or 200 mg/kg PC; and CdCl2 + 25 or 50 mg/kg DDMP. The rats were sacrificed 55 days after the start of the study; Samples were collected for analysis. Biochemical parameters malondialdehyde, nitric oxide, antioxidant enzymes, and proton pumps were measured by spectrophotometry. Reproductive hormones were measured using ELISA. Data were analysed using ANOVA and differences in mean values were considered significant at p<0.05. Significant increases in sperm count, motility, and viability were observed in the groups given CdCl2+Vitamin E, CdCl2+PC or CdCl2+DDMP as compared with the CdCl2 group. Malondialdehyde and nitric oxide levels in the groups treated with CdCl2+PC or CdCl2+DDMP decreased significantly when compared with the group given CdCl2. Significant increases were observed in antioxidant enzymes, proton pump, and testosterone in the groups treated with CdCl2+PC or CdCl2+DDMP, respectively. Plukenetia conophora alleviated male reproductive toxicity induced by cadmium chloride in Wistar rats. 4H-Pyran-4-One 2,3-Dihydro-3,5-Dihydroxy-6-Methyl present in Plukenetia conophora may be responsible for the ameliorative effects.

Background: It is estimated that about 5–10% of women suffer from polycystic ovarian syndrome (PCOS) which is a major cause of female reproductive dysfunction. This study examined the role of quercetin on dehydroepiandrosterone (DHEA)-induced PCO in Wistar rats. Methods: Twenty-eight pre-pubertal female Wistar rats that are 21 days old weighing 16–21 g were sorted into four groups (n = 7). Group I served as control and was given distilled water only, Group II were injected with 6 mg/100 g BW of DHEA in 0.2 mL of corn oil subcutaneously, Group III received 100 mg/kg BW of quercetin orally and Group IV received 6 mg/100 g BW of DHEA in 0.2 mL of corn oil subcutaneously and 100 mg/kg BW of quercetin orally. Rats were sacrificed after 15 days by cervical dislocation method. Blood samples and ovaries were collected for hormonal, biochemical, and histopathological analysis and expressions of mRNA androgen receptor gene were determined using RT–qPCR. All data were analysed using one-way ANOVA. Results: A significant decrease (p < 0.05) in the antioxidant and metabolic enzyme activity in the DHEA treated group was observed when compared with control. DHEA co-administration with quercetin showed a significant decrease in malondialdehyde and cytokines when compared with DHEA treated group. Also a significant increase in progesterone, metabolic and antioxidant enzyme activity was observed. The histopathology demonstrates a reduction in cystic and atretic cells, improved expression of BCl2, E-Cadherin and a decrease in Bax. Conclusions: Quercetin alleviated DHEA-induced PCO. These effects could be attributed to its antioxidant property.