Betulin, a pentacyclic triterpene and a plant pentacyclic triterpene metabolite, can be found in large quantities in the outer bark of the birches (Betula, Betulaceae). Betulinic acid, obtained by betulin oxidation, is also abundantly present in nature. Both compounds show a wide spectrum of biological and pharmacological properties, such as anti-HIV, anti-inflammatory, and, considered the most important, anti-cancer. Although the specific mechanism of action of betulin against malignant cells is still a subject of detailed research, the activity of betulin acid has been linked to the induction of the intrinsic pathway of apoptosis. As this process occurs with the sparing of non-cancer cells, and the induction of apoptosis can occur under conditions in which standard therapies fail, both substances seem as promising experimental anti-cancer drugs. The aim of this review is to comprehensively summarise the potential of betulin and betulinic acid, both in vitro and in vivo. The discovery, structure, organic synthesis and derivatives forming were shortly described. Also, the potential molecular mechanisms of action and numerous medical applications of betulin and betulinic acid were presented, including previous studies of anti-cancer activity of the compounds, with listed cancer cell types susceptible to therapy.
Aims The family of kynurenine pathway (KP) metabolites includes compounds produced along two arms of the path and acting in clearly opposite ways. The equilibrium between neurotoxic kynurenines, such as 3‐hydroxykynurenine (3‐HK) or quinolinic acid (QUIN), and neuroprotective kynurenic acid (KYNA) profoundly impacts the function and survival of neurons. This comprehensive review summarizes accumulated evidence on the role of KYNA in Alzheimer's, Parkinson's and Huntington's diseases, and discusses future directions of potential pharmacological manipulations aimed to modulate brain KYNA. Discussion The synthesis of specific KP metabolites is tightly regulated and may considerably vary under physiological and pathological conditions. Experimental data consistently imply that shift of the KP to neurotoxic branch producing 3‐HK and QUIN formation, with a relative or absolute deficiency of KYNA, is an important factor contributing to neurodegeneration. Targeting specific brain regions to maintain adequate KYNA levels seems vital; however, it requires the development of precise pharmacological tools, allowing to avoid the potential cognitive adverse effects. Conclusions Boosting KYNA levels, through interference with the KP enzymes or through application of prodrugs/analogs with high bioavailability and potency, is a promising clinical approach. The use of KYNA, alone or in combination with other compounds precisely influencing specific populations of neurons, is awaiting to become a significant therapy for neurodegenerative disorders.
Introduction. Terpenes are the largest known class of organic compounds, widely distributed in plants. They are grouped considering the number of isoprene units in their structure; hence, the group consisting of 30 carbon atoms is called triterpenes. These compounds have a wide range of biological features. Objective. The aim of this review was to comprehensively discuss the role of betulin and betulinic acid as potent anticancer agents, including various studies determining their efficiency in cancer treatment and enumerating the types of cancer susceptible to this kind of therapy. State of knowledge. Betulin is a naturally occurring lupane-type pentacyclic triterpene, wildly distributed in plants, especially Betulinaceae. One of its derivatives, formed by oxidation, is betulinic acid. Both compounds are abundantly present in the outer bark of white birch, with betulin forming up to 34% its dry mass and are known for their valuable biological properties, including anti-cancer effect. By inducing the internal apoptosis pathway in cancer cells while sparing normal cells, they are a great help in the treatment of most malignancies, alone or in combination with radio-or chemotherapy. Summary. Compounds that have a direct effect on mitochondria are promising experimental anticancer drugs, since they are able to cause cell death in conditions in which conventional therapies, including chemotherapeutics, usually fail. Therefore, mitochondrial targeting agents such as betulin and betulinic acid are a promise of a new therapeutic strategy for the treatment of human tumours.
In the article are considered issues related to the study of the effect of cadmium on the body of birds, in particular laying hens. The effect of cadmium sulfate at doses of 2.0 and 4.0 mg/kg body weight on protein synthesis function and functional state of the liver were investigated of cross-laying Hysex white hens, of 78 weeks old. Three groups of chickens were formed: two experimental and one control groups. The laying hens of the experimental groups were subjected to a cadmium load. Laying chickens of the first experimental group were given cadmium sulfate at a dose of 2.0 mg/kg body weight. Laying chickens of the second experimental group were given cadmium sulfate at a dose of 4.0 mg/kg body weight. Laying chickens in the control group were in the normal diet without cadmium. Increased activity of aminotransferases, in particular alanine and aspartate aminotransferases in their serum of hens, was observed during cadmium binge drinking in doses of 2.0 and 4.0 mg/kg body weight, respectively. These changes indicate a violation of the functional state of the liver of laying hens under conditions of cadmium load. In the study of protein synthesis of the liver of laying hens under conditions of cadmium loading, it was found that cadmium sulfate in the above doses contributed to a significant decrease in the level of total protein by 14, 21 and 30 days of the experiment. The reduction of total protein in the blood of laying hens was due to a decrease in the level of albumin, which in the second experimental group, respectively, decreased to 28.16 ± 0.75%, whereas in the first – 29.62 ± 0.98%. In the study of the level of globulins, it is possible to increase this indicator in both experimental groups of poultry for 21 days. Drinking with water cadmium sulfate at a dose of 4.0 mg/kg body weight was associated with a more likely decrease in total protein and albumin than drinking cadmium sulfate at a lower dose.
Silver birch, Betula pendula Roth, is one of the most common trees in Europe. Due to its content of many biologically active substances, it has long been used in medicine and cosmetics, unlike the rare black birch, Betula obscura Kotula. The aim of the study was therefore to compare the antioxidant properties of extracts from the inner and outer bark layers of both birch trees towards the L929 line treated with acetaldehyde. Based on the lactate dehydrogenase test and the MTT test, 10 and 25% concentrations of extracts were selected for the antioxidant evaluation. All extracts at tested concentrations reduced the production of hydrogen peroxide, superoxide anion radical, and 25% extract decreased malonic aldehyde formation in acetaldehyde-treated cells. The chemical composition of bark extracts was accessed by IR and HPLC-PDA methods and surprisingly, revealed a high content of betulin and lupeol in the inner bark extract of B. obscura. Furthermore, IR analysis revealed differences in the chemical composition of the outer bark between black and silver birch extracts, indicating that black birch may be a valuable source of numerous biologically active substances. Further experiments are required to evaluate their potential against neuroinflammation, cancer, viral infections, as well as their usefulness in cosmetology.
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