Nejvíce citovaný článek - PubMed ID 30703480
The influence of alkaloids on oxidative stress and related signaling pathways
Background: Chlorophytum borivilianum L. is a recognized herbal medicine for the management of impotency in South Asian countries. In Ayurveda, it is used for the management of multiple health conditions, including diabetes, infection, and cardiovascular diseases. Parts of the plant have been used as excellent antioxidants and scavengers of free radicals. Since oxidative stress plays an important role in spermatogenesis and fertility in male populations, this study evaluated the role of ethanolic extract of C. borivilianum roots in epididymal sperm maturation against adversities posed by ionizing gamma irradiation. Materials and methods: Antioxidant potential of C. borivilianum root extract (CRE) was evaluated through DPPH (2,2-diphenylpicrylhydrazyl) and NO (nitric oxide) scavenging assays. Four groups of healthy Swiss albino mice were constituted, which were labeled as follows: Group I: sham control, Group II: 7-day pre-treatment with 50 mg/kg CRE, Group III: 6 Gy irradiation without pre-treatment, and Group IV: 7-day pre-treatment with 50 mg/kg CRE and 6 Gy irradiation on day 7. Swiss albino mice were observed for 30 days and later sacrificed to evaluate sperm quality parameters. Results: CRE showed a remarkable antioxidant potential with IC50 values of 46.37 μg/ml and 98.39 μg/ml for DPPH and NO, respectively. A significant decline (p < 0.001) in cauda epididymal sperm count, motility, and viability was observed in Group III animals. Group IV also showed a substantial decline (p < 0.01) in all three parameters compared to Group I; nonetheless, these were significantly higher than Group III. Morphological alterations indicated a coiled and bent tail, with the presence of cytoplasmic droplets in Group III, which declined substantially in Group IV. The ultrastructure of sperm indicated higher curvature of hook in Group III than Group IV, indicating specific interferences in the sperm maturation process. Conclusion: It was concluded that pre-treatment with 50 mg/kg body weight of CRE could protect sperm during epididymal maturation against oxidative stress.
- Klíčová slova
- Chlorophytum borivilianum, male fertility, oxidative stress, sperm characteristics, sperm maturation,
- Publikační typ
- časopisecké články MeSH
Data on alkaloid interactions with the physiologically important transition metals, iron and copper, are mostly lacking in the literature. However, these interactions can have important consequences in the treatment of both Alzheimer's disease and cancer. As isoquinoline alkaloids include galanthamine, an approved drug for Alzheimer's disease, as well as some potentially useful compounds with cytostatic potential, 28 members from this category of alkaloids were selected for a complex screening of interactions with iron and copper at four pathophysiologically relevant pH and in non-buffered conditions (dimethyl sulfoxide) by spectrophotometric methods in vitro. With the exception of the salts, all the alkaloids were able to chelate ferrous and ferric ions in non-buffered conditions, but only five of them (galanthine, glaucine, corydine, corydaline and tetrahydropalmatine) evoked some significant chelation at pH 7.5 and only the first two were also active at pH 6.8. By contrast, none of the tested alkaloids chelated cuprous or cupric ions. All the alkaloids, with the exception of the protopines, significantly reduced the ferric and cupric ions, with stronger effects on the latter. These effects were mostly dependent on the number of free aromatic hydroxyls, but not other hydroxyl groups. The most potent reductant was boldine. As most of the alkaloids chelated and reduced the ferric ions, additional experimental studies are needed to elucidate the biological relevance of these results, as chelation is expected to block reactive oxygen species formation, while reduction could have the opposite effect.
- Klíčová slova
- alkaloid, chelation, copper, iron, reduction,
- MeSH
- Alzheimerova nemoc * MeSH
- chelátory chemie MeSH
- cytostatické látky * MeSH
- dimethylsulfoxid MeSH
- galantamin MeSH
- hydroxylový radikál MeSH
- isochinoliny farmakologie MeSH
- lidé MeSH
- měď chemie MeSH
- reaktivní formy kyslíku MeSH
- redukční činidla MeSH
- soli MeSH
- železo chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chelátory MeSH
- cytostatické látky * MeSH
- dimethylsulfoxid MeSH
- galantamin MeSH
- hydroxylový radikál MeSH
- isochinoliny MeSH
- měď MeSH
- reaktivní formy kyslíku MeSH
- redukční činidla MeSH
- soli MeSH
- železo MeSH
Flavonoids are associated with positive cardiovascular effects. However, due to their low bioavailability, metabolites are likely responsible for these properties. Recently, one of these metabolites, 4-methylcatechol, was described to be a very potent antiplatelet compound. This study aimed to compare its activity with its 22 close derivatives both of natural or synthetic origin in order to elucidate a potential structure-antiplatelet activity relationship. Blood from human volunteers was induced to aggregate by arachidonic acid (AA), collagen or thrombin, and plasma coagulation was also studied. Potential toxicity was tested on human erythrocytes as well as on a cancer cell line. Our results indicated that 17 out of the 22 compounds were very active at a concentration of 40 μM and, importantly, seven of them had an IC50 on AA-triggered aggregation below 3 μM. The effects of the most active compounds were confirmed on collagen-triggered aggregation too. None of the tested compounds was toxic toward erythrocytes at 50 μM and four compounds partly inhibited proliferation of breast cancer cell line at 100 μM but not at 10 μM. Additionally, none of the compounds had a significant effect on blood coagulation or thrombin-triggered aggregation. This study hence reports four phenol derivatives (4-ethylcatechol, 4-fluorocatechol, 2-methoxy-4-ethylphenol and 3-methylcatechol) suitable for future in vivo testing.
- Klíčová slova
- 4-methylcatechol, aggregation, catechol, flavonoid, platelet, whole blood,
- MeSH
- agregace trombocytů * MeSH
- fenol * MeSH
- fenoly farmakologie MeSH
- inhibitory agregace trombocytů farmakologie MeSH
- lidé MeSH
- trombin farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fenol * MeSH
- fenoly MeSH
- inhibitory agregace trombocytů MeSH
- trombin MeSH