Search

Human Papillomavirus (HPV) infection represents a global health concern. HPV infects the mucosa, particularly in the uterine cervix, where it may establish a persistent infection, exposing women to a risk of developing cancer. The available treatments include surgery or topic solutions, while a systemic treatment is still unavailable. In recent years, natural molecules such as epigallocatechin gallate (EGCG), folic acid (FA), vitamin B12, and hyaluronic acid (HA) gained importance as innovative therapies for HPV. We enrolled 163 women with a positive HPV DNA test or previous history of HPV infections, and a PAP test indicating LSIL/AGUS/ASCUS cytology. The patients in the treatment group (n = 86) received an oral combination of EGCG 200 mg, FA 400 µg, vitamin B12 1 mg, and HA 50 mg (1 cps/day) for 3 months (T1), while the control group (n = 77) underwent standard clinical surveillance. Both groups repeated a PAP test and an HPV DNA test after 3 (T1) months, and another PAP test after 6 months (T2) as a follow up. The treatment group experienced a significant reduction in HPV positivity at T1 compared to the control group. Moreover, the treatment group exhibited an improvement in cervical lesions either at T1 (p < 0.0001) or T2 (p < 0.00001).

D-chiro-inositol (DCI) is a natural compound detectable in cell membranes, which is highly conserved as a biological signaling molecule. In mammals, its function is primarily characterized in the intracellular transduction cascade of insulin. In particular, insulin signal promotes the release of pivotal DCI-containing molecules. In fact, impaired release of DCI is a common feature of insulin-resistant tissues, and insulin-sensitizing pharmaceuticals induce higher concentrations of free DCI. Moreover, it also plays important roles in several other processes. DCI is involved in the regulation of steroidogenesis, due to its regulatory effects on steroidogenic enzymes, including 17α-hydroxylase, 3β-hydroxysteroid dehydrogenase, and aromatase. Such regulation of various enzymes indicates a mechanism by which the body regulates different processes via a single molecule, depending on its concentration. DCI also reduces the expression of integrin β3, which is an adhesion molecule involved in embryo implantation and cellular phenomena such as survival, stemness, and invasiveness. In addition, DCI seems to have important anti-inflammatory activities, like its 3-O-methyl-ether, called pinitol. In vitro evidence demonstrates that treatment with both compounds induces a reduction in pro-inflammatory factors—such as Nf-κB—and cytokines—such as TNF-α. DCI then plays important roles in several fundamental processes in physiology. Therefore, research on such molecule is of primary importance.

Infertility is defined as a couple’s inability to conceive after at least one year of regular unprotected intercourse. This condition has become a global health problem affecting approximately 187 million couples worldwide and about half of the cases are attributable to male factors. Oxidative stress is a common reason for several conditions associated with male infertility. High levels of reactive oxygen species (ROS) impair sperm quality by decreasing motility and increasing the oxidation of DNA, of protein and of lipids. Multi-antioxidant supplementation is considered effective for male fertility parameters due to the synergistic effects of antioxidants. Most of them act by decreasing ROS concentration, thus improving sperm quality. In addition, other natural molecules, myo-inositol (MI) and d-chiro–inositol (DCI), ameliorate sperm quality. In sperm cells, MI is involved in many transduction mechanisms that regulate cytoplasmic calcium levels, capacitation and mitochondrial function. On the other hand, DCI is involved in the downregulation of steroidogenic enzyme aromatase, which produces testosterone. In this review, we analyze the processes involving oxidative stress in male fertility and the mechanisms of action of different molecules.

Pregnancy is a complex process, featuring several necessary changes in women’s physiology. Most women undergo healthy pregnancies; even so, several women experience reduced fertility or pathologies related to the pregnancy. In the last years, researchers investigated several molecules as promoters of fertility. Among all, myo-inositol (myo-ins) represents a safe compound that proved useful in issues related to fertility and pregnancy. In fact, myo-ins participates in several signaling processes, including the pathways of insulin and gonadotropins, and, therefore, it is likely to positively affect fertility. In particular, several clinical trials demonstrate that its administration can have therapeutic effects in infertile women, and that it can also be useful as a preventive treatment during pregnancy. Particularly, myo-ins could prevent the onset of neural tube defects and the occurrence of gestational diabetes mellitus, promoting a trouble-free gestation. Due to the safety and efficiency of myo-ins, such a treatment may also substitute several pharmaceuticals, which are contraindicated in pregnancy.