ROLE OF PHYTOESTROGENS IN PREVENTION OF OSTEOPOROSIS

Osteoporosis is a disease characterized with the disbalance between the bone-building activity of osteoblasts and the re absorptive activity of osteoclasts. Estrogen deficiency occurring after menopause leads to enhanced risk of sudden fractures due to reduced bone mass. Phytoestrogens are polyphenolic plant metabolites: isoflavonoids, flavonoids (flavones, flavanones, chalcones), lignans, stilbenes. Phytoestrogens possess estrogenic activity and display the higher affinity for β-estrogen receptor due to their structural similarity to 17β-Estradiol. It is reported that bone loss is suppressed by Genistein and Daidzein from soy products, Quercetin and Rutin, Resveratrol from grapes and red wine, Kaempferol and Apigenin, Hesperidin, (+)-Catechin and Epigallocatechin gallate from green tea and Oleuropein. The most effective isoflavone in preserving bone health appears to be Genistein, which stimulates osteoblast and inhibits osteoclast function. Osteo protective effect of Formononetin on skeletal system results from the inhibition of osteoclastogenesis. Effects of Coumestrol on osteoblasts and osteoclasts are in increasing the bone density and preventing of bone resorption. Bioactive flavonoids enhance bone formation and inhibit bone resorption through their action on cell signaling pathways that influence osteoblast and osteoclast differentiation. 8-Prenylnaringenin promotes osteoblastic differentiation and inhibits bone resorption activity of osteoclasts by inducing ot their apoptosis. Plant lignans have been shown to provide estrogenic support, antioxidant and anti-inflammatory activity. Stilbene antioxidant Resveratrol exerts potential to attenuate bone loss due to multiple actions on both osteoblasts and osteoclasts. Monoterpene components from essential oils protects from bone loss. Due to inhibitory of the osteoclast activity

Creatine lysinate – part II: effects on the motor coordination and muscle hypertrophy in mice

In the current study, we investigated the effect of creatine monohydrate (CrM) and newly synthesized creatine lysinate (CrLys) in tail suspension (TST) and rotarod tests and their influence on the histology of the skeletal muscles. In the TST, a slight decrease in the immobility time from the 1st to the 3rd week was observed in the group treated with CrM at a dose of 1.5 g/kg/day and CrLys at a dose of 6 g/kg/day. The rotarod test revealed that CrM (1.5 g/kg/day) and CrLys (3 g/kg/day) lead to a significant improvement in motor coordination in the 3rd week. The results from histology showed an increase in the muscle fiber diameter of soleus muscle in animals treated with CrM (3 g/kg/day) and CrLys (6 g/kg/day). The results showed that supplementation with creatine derivatives appears to be a generally effective nutritional ergogenic aid for an improvement of physical performance

Creatine lysinate – part I: investigation of the toxicity and the influence on some biochemical parameters in mice

In our study we investigated the acute toxicity of а newly synthesized creatine lysinate as well as its effect on the biochemical parameters in mice. Creatine lysinate exerts better solubility in water (3.3%) in comparison to creatine monohydrate (1.4%) at 20 °C and it is determined as a non-toxic after intraperitoneal (LD50 – 4543 mg/kg) and oral administration (LD50 > 8000 mg/kg). Oral administration of creatine lysinate at doses of 3 g/kg/day and 6 g/kg/day for 2 weeks reduced the creatine kinase levels, which indicates muscle protection. An increased levels of liver enzymes like alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) was observed after the supplementation with creatine lysinate at both administered doses and the level of lactate was comparable both in the studied and the control group

Application of Approved Cisplatin Derivatives in Combination Therapy against Different Cancer Diseases

The problems with anticancer therapy are resistance and toxicity. From 3000 Cisplatin derivatives tested as antitumor agents, most of them have been rejected, due to toxicity. The aim of current study is the comparison of therapeutic combinations of the currently applied in clinical practice: Cisplatin, Carboplatin, Oxaliplatin, Nedaplatin, Lobaplatin, Heptaplatin, and Satraplatin. The literature data show that the strategies for the development of platinum anticancer agents and bypassing of resistance to Cisplatin derivatives and their toxicity are: combination therapy, Pt IV prodrugs, the targeted nanocarriers. The very important strategy for the improvement of the antitumor effect against different cancers is synergistic combination of Cisplatin derivatives with: (1) anticancer agents—Fluorouracil, Gemcitabine, Cytarabine, Fludarabine, Pemetrexed, Ifosfamide, Irinotecan, Topotecan, Etoposide, Amrubicin, Doxorubicin, Epirubicin, Vinorelbine, Docetaxel, Paclitaxel, Nab-Paclitaxel; (2) modulators of resistant mechanisms; (3) signaling protein inhibitors—Erlotinib; Bortezomib; Everolimus; (4) and immunotherapeutic drugs—Atezolizumab, Avelumab, Bevacizumab, Cemiplimab, Cetuximab, Durvalumab, Erlotinib, Imatinib, Necitumumab, Nimotuzumab, Nivolumab, Onartuzumab, Panitumumab, Pembrolizumab, Rilotumumab, Trastuzumab, Tremelimumab, and Sintilimab. An important approach for overcoming the drug resistance and reduction of toxicity of Cisplatin derivatives is the application of nanocarriers (polymers and liposomes), which provide improved targeted delivery, increased intracellular penetration, selective accumulation in tumor tissue, and enhanced therapeutic efficacy. The advantages of combination therapy are maximum removal of tumor cells in different phases; prevention of resistance; inhibition of the adaptation of tumor cells and their mutations; and reduction of toxicity

Regulation and control of the use of Cannabis and Cannabidiol in „novel foods”

Cannabis sativa L. is a medicinal plant from family Cannabaceae with many pharmacological activities. The recent appearance of a number of cannabis products in the pharmaceutical market has led to increased requirements for regulation and quality control. The control of Cannabis sativa L. is subject to the Psychotropic Substances Convention, which includes the addictive psychoactive delta-9-tetrahydrocannabinol (THC), and to the Narcotic Drugs Convention, which includes the illicit products: herbal and liquid cannabis, resin, extracts and tinctures of flowering or fruiting tops containing THC. Approved by the FDA for use in chemotherapy are Marinol caps. (THC) and Cesamet caps., containing the synthetic THC-derivative Nabilon. There is no harmonized European Union legislation on the use of cannabis and Cannabidiol (CBD), which antagonizes the THC-psychotropic effect. Legitimate products include seeds, oil, extracts, and seed tinctures of the industrial cannabis chemotype, containing primarily Cannabidiol and less than 0.2% THC. Sativex oral spray (THC/CBD = 1:1) is approved for muscle spasticity in multiple sclerosis. Cannabidiol was not used as a food ingredient in the European Union before 15.05.1997 and is a „novel food” according to Regulation 2015/2283. Flour; protein powder and cannabis seed oil are not „novel foods”. Cannabidiol as Epidiolex is FDA approved for epilepsy forms Lennox-Gastaut and Dravet

Regulation and control of the use of Cannabis and Cannabidiol in „novel foods”

Cannabis sativa L. is a medicinal plant from family Cannabaceae with many pharmacological activities. The recent appearance of a number of cannabis products in the pharmaceutical market has led to increased requirements for regulation and quality control. The control of Cannabis sativa L. is subject to the Psychotropic Substances Convention, which includes the addictive psychoactive delta-9-tetrahydrocannabinol (THC), and to the Narcotic Drugs Convention, which includes the illicit products: herbal and liquid cannabis, resin, extracts and tinctures of flowering or fruiting tops containing THC. Approved by the FDA for use in chemotherapy are Marinol caps. (THC) and Cesamet caps., containing the synthetic THC-derivative Nabilon. There is no harmonized European Union legislation on the use of cannabis and Cannabidiol (CBD), which antagonizes the THC-psychotropic effect. Legitimate products include seeds, oil, extracts, and seed tinctures of the industrial cannabis chemotype, containing primarily Cannabidiol and less than 0.2% THC. Sativex oral spray (THC/CBD = 1:1) is approved for muscle spasticity in multiple sclerosis. Cannabidiol was not used as a food ingredient in the European Union before 15.05.1997 and is a „novel food” according to Regulation 2015/2283. Flour; protein powder and cannabis seed oil are not „novel foods”. Cannabidiol as Epidiolex is FDA approved for epilepsy forms Lennox-Gastaut and Dravet