Introduction: Propolis has a wide range of biological and pharmacological actions, including antioxidant properties-particularly its phenolic and flavonoid constituents-that could potentially protect the reproductive system from oxidative damage. Method: Four groups were allocated 40 male Wistar rats each. The vehicle was given to the first group's normal control rats negative control. The second, third, and fourth groups of diabetic rats were given vehicle (diabetic control) and propolis orally at 50 and 100 mg/kg, respectively, for 8 weeks. Diabetes was induced in rats via injection of nicotinamide and streptozotocin (STZ). Fasting blood glucose (FBG) and insulin levels, homeostatic model assessment for insulin resistance (HOMA-IR), and semen analysis were assessed. In addition, assessments of serum reproductive hormones, including total testosterone (TTST), estradiol (E2), follicle-stimulating hormone luteinizing hormone (LH), and prolactin (PRL), were measured at the end of the study. Tissue total testosterone, E2, and dihydrotestosterone were also evaluated. Serum and tissue oxidative enzymes, including catalase (CAT), superoxide dismutase, and glutathione peroxidase activities, were examined, and malondialdehyde content was determined. The pancreatic and testicular tissues were histopathologically examined, and proliferating cell nuclear antigen (PCNA) and B-cell lymphoma 2 (Bcl-2) in testicular tissue were immunohistochemically analyzed. Testicular tissue was examined for DNA integrity using a comet assay. Results: Compared to the STZ-control group, propolis greatly decreased FBG levels and improved the glycemic status of diabetic rats. In comparison to the STZ-DC group, propolis increased the number of sperm cells and the percent of morphologically normal and viable sperm in male rats, improving their fertility. Propolis also restored the pancreatic islets, protected the testis from oxidative stress, and increased levels of reproductive hormones in the blood, especially testosterone. Moreover, propolis at high doses demonstrated a strong positive response for Bcl-2 and a negative expression of proliferating cell nuclear antigen in spermatogenic cells. Conclusion: The data obtained strongly indicate that STZ causes severe impairments to the testis whereas propolis, acting as an antioxidant, protects against the adverse effects of STZ on the testis.

Scientific research is crucial to develop therapies for various disease severity levels, as modern drugs cause side effects and are difficult to predict. Researchers are exploring herbal alternatives with fewer side effects, particularly propolis, which has been validated through in vitro, in vivo, and clinical studies. This will focus on scientific evidence and its supporting technology for developing new bioactive compounds for chronic diseases. Nanotechnology can improve the delivery and absorption of herbal medicines, which often have poor bioavailability due to their high molecular weight and solubility in water, particularly in oral medicines. This technology can enhance propolis's effects through multi-target therapy and reduce side effects.

All publications related to each section of this review were discovered using the search engines Google Scholar, Scopus, and Pubmed. This was only available for publication between 2013 and 2023. The selected publications were used as references in this review after being thoroughly studied.

Evaluation of propolis active compounds, the classification of propolis nano formulations, design concepts, and mechanisms of action of propolis nano formulation. Additionally, the challenges and prospects for how these insights can be translated into clinical benefits are discussed.

In the last ten years, a list of nanoformulation propolis has been reported. This review concludes the difficulties encountered in developing large-scale nanoformulations. To commercialize them, improvements in nano carrier synthesis, standardized evaluation methodology within the framework of strategy process improvement, and Good Manufacturing Practices would be required.

Significance: Currently 10%-15% of couples in reproductive age face infertility issues. More importantly, male factor contributes to 50% of these cases (either alone or in combination with female causes). Among various reasons, impaired sperm function is the main cause for male infertility. Furthermore, mitochondrial dysfunction and oxidative stress due to increased reactive oxygen species (ROS) production, particularly of mitochondrial origin, are believed to be the main contributors. Recent Advances: Mitochondrial dysfunction, particularly due to increased ROS production, has often been linked to impaired sperm function/quality. For decades, different methods and approaches have been developed to assess mitochondrial features that might correlate with sperm functionality. This connection is now completely accepted, with mitochondrial functionality assessment used more commonly as a readout of sperm functionality. More recently, mitochondria-targeted compounds are on the frontline for both assessment and therapeutic approaches. Critical Issues: In this review, we summarize the current methods for assessing key mitochondrial parameters known to reflect sperm quality as well as therapeutic strategies using mitochondria-targeted antioxidants aiming to improve sperm function in various situations, particularly after sperm cryopreservation. Future Directions: Although more systematic research is needed, mitochondria-targeted compounds definitely represent a promising tool to assess as well as to protect and improve sperm function. Antioxid. Redox Signal. 37, 451-480.

This review aims to analyze propolis as a potential raw material for the development and manufacture of new health-promoting products. Many scientific publications were retrieved from the Scopus, PubMed, and Google Scholar databases via searching the word "propolis". The different extraction procedures, key biologically active compounds, biological properties, and therapeutic potential of propolis were analyzed. It was concluded that propolis possesses a variety of biological properties because of a very complex chemical composition that mainly depends on the plant species visited by bees and species of bees. Numerous studies found versatile pharmacological activities of propolis: antimicrobial, antifungal, antiviral, antioxidant, anticancer, anti-inflammatory, immunomodulatory, etc. In this review, the composition and biological activities of propolis are presented from a point of view of the origin and standardization of propolis for the purpose of the development of new pharmaceutical products on its base. It was revealed that some types of propolis, especially European propolis, contain flavonoids and phenolic acids, which could be markers for the standardization and quality evaluation of propolis and its preparations. One more focus of this paper was the overview of microorganisms' sensitivity to propolis for further development of antimicrobial and antioxidant products for the treatment of various infectious diseases with an emphasis on the illnesses of the oral cavity. It was established that the antimicrobial activity of different types of propolis is quite significant, especially to Gram-negative bacteria and lipophilic viruses. The present study could be also of interest to the pharmaceutical industry as a review for the appropriate design of standardized propolis preparations such as mouthwashes, toothpastes, oral drops, sprays, creams, ointments, suppositories, tablets, and capsules, etc. Moreover, propolis could be regarded as a source for the isolation of biologically active substances. Furthermore, this review can facilitate partially overcoming the problem of the standardization of propolis preparations, which is a principal obstacle to the broader use of propolis in the pharmaceutical industry. Finally, this study could be of interest in the area of the food industry for the development of nutritionally well-balanced products. The results of this review indicate that propolis deserves to be better studied for its promising therapeutic effects from the point of view of the connection of its chemical composition with the locality of its collection, vegetation, appropriate extraction methods, and standardization.

Bee products are sources of functional food that have been used in complementary medicine to treat a variety of acute and chronic illnesses in many parts of the world. The products vary from location to location as well as country to country. Therefore, the aim of this review was to identify various bee products with potential preventive and therapeutic values used in the treatment of male reproductive impairment. We undertook a vigorous search for bee products with preventive and therapeutic values for the male reproductive system. These products included honey, royal jelly, bee pollen, bee brood, apilarnil, bee bread, bee wax, and bee venom. We also explained the mechanisms involved in testicular steroidogenesis, reactive oxygen species, oxidative stress, inflammation, and apoptosis, which may cumulatively lead to male reproductive impairment. The effects of bee pollen, bee venom, honey, propolis, royal jelly, and bee bread on male reproductive parameters were examined. Conclusively, these bee products showed positive effects on the steroidogenic, spermatogenic, oxidative stress, inflammatory, and apoptotic parameters, thereby making them a promising possible preventive and therapeutic treatment of male sub/infertility.

Paclitaxel (taxol) is one of the most powerful anticancer drugs but it possesses toxic effects on male reproductive system. Propolis, from folkloric remedy, have antioxidant, anti-inflammatory and anticancer effects. The present study established to examine the protective impact of Propolis against malformation of semen induced by taxol. Twenty-four male rats equally divided into four groups. Group I (normal control); group II, administrated Propolis alone; group III, taxol-treated group received taxol; group IV, co-administered of taxol and Propolis extract. After 4 weeks of treatment, the semen were collected and testis 24 hr after the last treatment. Sperm count, motility, viability and sperm morphology were assayed. Tissue supernatants were isolated for oxidative stress, cell energy parameters and 8-OHdG. DNA damage was evaluated using Comet assay in testes. Our results confirmed that taxol-induced significant reduction in sperm count, motility, viability and recorded marked elevation in sperm abnormalities. Also, taxol caused increased in 8-OHdG and DNA damage versus that recorded in control group. Treatment with Propolis improving semen quality and protected testis from detrimental effects of taxol and minimises its toxicity. In conclusions, Oral administration of Propolis modulates the toxic impact of taxol by amelioration semen quality, diminishing oxidation state, DNA damage and preserving cell energy.

The propolis extract was shown to possess the capacity to protect sperm membrane from the deleterious action of oxidative attack. Oxidative stress can induce propagation of a lipid peroxidation (LPO) chain reaction because spermatozoa contain high concentration of unsaturated fatty acids. This study aimed at evaluating in vitro the possible toxicity and/or the antioxidant properties of Propolfenol^® in ejaculated human spermatozoa. A colorimetric assay determined the total flavonoid content by spectrophotometry and a high-performance liquid chromatography-diode array detection analysis the quantity of galangin, pinocembrin and caffeic acid phenylethilic ester (CAPE). Sperm parameters such as motility, vitality and DNA integrity were assessed utilising optical microscopy. The antioxidant properties Propolfenol^® against LPO induced by tert-Butyl Hydroperoxide were evaluated using the C11-BODIPY581/591 probe. Chemical analysis of Propolfenol^® revealed low quantities of galangin, pinocembrin and CAPE; cyclic voltammetry experiments showed that Propolfenol^® may exert an antioxidant activity. A protective action of Propolfenol^® (20 and 100 μg/ml) on induced LPO in human spermatozoa was detected. Propolfenol^® may be proposed as the supplement in media for sperm preparation techniques or cryopreservation to counteract the increased presence of reactive oxygen species generated by these methods.

Blood mononuclear cells consist of T cells and monocyte derived cells. Beside immunity, the blood mononuclear cells belong to the complex tissue control system (TCS), where they exhibit morphostatic function by stimulating proliferation of tissue stem cells followed by cellular differentiation, that is stopped after attaining the proper functional stage, which differs among various tissue types. Therefore, the term immune and morphostatic system (IMS) should be implied. The TCS-mediated morphostasis also consists of vascular pericytes controlled by autonomic innervation, which is regulating the quantity of distinct tissues in vivo. Lack of proper differentiation of tissue cells by TCS causes either tissue underdevelopment, e.g., muscular dystrophy, or degenerative functional failures, e.g., type 1 diabetes and age-associated diseases. With the gradual IMS regression after 35 years of age the gonadal infertility develops, followed by a growing incidence of age-associated diseases and cancers. Without restoring an altered TCS function in a degenerative disease, the implantation of tissue-specific stem cells alone by regenerative medicine can not be successful. Transfused young blood could temporarily restore fertility to enable parenthood. The young blood could also temporarily alleviate aging diseases, and this can be extended by substances inducing IMS regeneration, like the honey bee propolis. The local and/or systemic use of honey bee propolis stopped hair and teeth loss, regressed varicose veins, improved altered hearing, and lowered high blood pressure and sugar levels. Complete regression of stage IV ovarian cancer with liver metastases after a simple elaborated immunotherapy is also reported.

In vitro maturation (IVM) and in vitro fertilization (IVF) technologies are facing with growing demands of older women to conceive. Although ovarian stem cells (OSCs) of older women are capable of producing in vitro fresh oocyte-like cells (OLCs), such cells cannot respond to IVM and IVF due to the lack of granulosa cells required for their maturation. Follicular renewal is also dependent on support of circulating blood mononuclear cells. They induce intermediary stages of meiosis (metaphase I chromosomal duplication and crossover, anaphase, telophase, and cytokinesis) in newly emerging ovarian germ cells, as for the first time demonstrated here, induce formation of granulosa cells, and stimulate follicular growth and development. A pretreatment of OSC culture with mononuclear cells collected from blood of a young healthy fertile woman may cause differentiation of bipotential OSCs into both developing germ and granulosa cells. A small blood volume replacement may enable treatment of ovarian infertility in vivo. The transferred mononuclear cells may temporarily rejuvenate virtually all tissues, including improvement of the function of endocrine tissues. Formation of new follicles and their development may be sufficient for IVM and IVF. The novel proposed in vitro approaches may be used as a second possibility. Infertility of human males affects almost a half of the infertility cases worldwide. Small blood volume replacement from young healthy fertile men may also be easy approach for the improvement of sperm quality in older or other affected men. In addition, body rejuvenation by small blood volume replacement from young healthy individuals of the same sex could represent a decline of in vitro methodology in favor of in vivo treatment for human functional diseases. Here we propose for the first time that blood mononuclear cells are essential for rejuvenation of those tissues, where immune system components participate in an appropriate division and differentiation of tissue stem cells. If needed, small blood volume replacement from distinct young healthy individuals could be utilized in six month intervals for repair of young altered or aged reproductive and other tissue functions. Systemic and local use of honey bee propolis tincture is an alternative option for functional rejuvenation of some tissues.