Activities and Molecular Mechanisms of Diterpenes, Diterpenoids, and Their Derivatives in Rheumatoid Arthritis.

Diterpenes and their derivatives have many biological activities, including anti-inflammatory and immunomodulatory effects. To date, several diterpenes, diterpenoids, and their laboratory-derived products have been demonstrated for antiarthritic activities. This study summarizes the literature about diterpenes and their derivatives acting against rheumatoid arthritis (RA) depending on the database reports until 31 August 2021. For this, we have conducted an extensive search in databases such as PubMed, Science Direct, Google Scholar, and Clinicaltrials.gov using specific relevant keywords. The search yielded 2708 published records, among which 48 have been included in this study. The findings offer several potential diterpenes and their derivatives as anti-RA in various test models. Among the diterpenes and their derivatives, andrographolide, triptolide, and tanshinone IIA have been found to exhibit anti-RA activity through diverse pathways. In addition, some important derivatives of triptolide and tanshinone IIA have also been shown to have anti-RA effects. Overall, findings suggest that these substances could reduce arthritis score, downregulate oxidative, proinflammatory, and inflammatory biomarkers, modulate various arthritis pathways, and improve joint destruction and clinical arthritic conditions, signs, symptoms, and physical functions in humans and numerous experimental animals, mainly through cytokine and chemokine as well as several physiological protein interaction pathways. Taken all together, diterpenes, diterpenoids, and their derivatives may be promising tools for RA management.

Chemotherapeutic and Safety Profile of a Fraction from Mimosa caesalpiniifolia Stem Bark.

Mimosa caesalpiniifolia (Fabaceae) is used by Brazilian people to treat hypertension, bronchitis, and skin infections. Herein, we evaluated the antiproliferative action of the dichloromethane fraction from M. caesalpiniifolia (DFMC) stem bark on murine tumor cells and the in vivo toxicogenetic profile. Initially, the cytotoxic activity of DFMC on primary cultures of Sarcoma 180 (S180) cells by Alamar Blue, trypan, and cytokinesis block micronucleus (CBMN) assays was assessed after 72 h of exposure, followed by the treatment of S180-bearing Swiss mice for 7 days, physiological investigations, and DNA/chromosomal damage. DFMC and betulinic acid revealed similar in vitro antiproliferative action on S180 cells and induced a reduction in viable cells, induced a reduction in viable cells and caused the emergence of bridges, buds, and morphological features of apoptosis and necrosis. S180-transplanted mice treated with DFMC (50 and 100 mg/kg/day), a betulinic acid-rich dichloromethane, showed for the first time in vivo tumor growth reduction (64.8 and 80.0%) and poorer peri- and intratumor quantities of vessels. Such antiproliferative action was associated with detectible side effects (loss of weight, reduction of spleen, lymphocytopenia, and neutrophilia and increasing of GOT and micronucleus in bone marrow), but preclinical general anticancer properties of the DFMC were not threatened by toxicological effects, and these biomedical discoveries validate the ethnopharmacological reputation of Mimosa species as emerging phytotherapy sources of lead molecules.

Ascorbic acid and retinol palmitate modulatory effect on omeprazole-induced oxidative damage, and the cytogenetic changes in S. cerevisiae and S180 cells.

Omeprazole (OM), a prototype proton pump inhibitor, oxidizes thiol groups and induces DNA damage. The aim of this study was to evaluate the oxidative effects of omeprazole and its interactions with ascorbic acid (AA, 50 µM) and retinol palmitate (RP) in proficient and deficient Saccharomyces cerevisiae strains, as well as levels of cytogenetic damage in Sarcoma 180 (S180) cells. Omeprazole was tested at concentrations of 10, 20 and 40 µg/mL, whereas H2O2 (10 mM), cyclophosphamide (20 mg/mL), and saline (0.9% NaCl solution) were employed as stressor, positive control, and negative control, respectively. Results revealed that omeprazole concentration-dependently induces oxidative effects in S. cerevisiae strains. However, omeprazole co-treated with ascorbic acid (50 µM) and retinol palmitate (100 IU) significantly modulated the oxidative damage inflected on the S. cerevisiae strains. Furthermore, omeprazole did not produce micronucleus formation and chromosomal bridges in S180 cells, but induced shoots. Significant increase in karyolysis and karyorrhexis were also observed with the omeprazole treated groups, which was modulated by co-treatment with ascorbic acid and retinol palmitate. Taken all together, it is suggested that ascorbic acid and retinol palmitate can substantially modulate the oxidative damage caused by omeprazole on the S. cerevisiae strains, however, much precaution is recommended with omeprazole and antioxidant co-treatment.

Assessment of Grape, Plum and Orange Synthetic Food Flavourings Using in vivo Acute Toxicity Tests.

The present study evaluates the acute toxicity of synthetic grape, plum and orange flavourings in root meristem cells of Allium cepa at the doses of 3.5, 7.0 and 14.0 mL/kg and exposure times of 24 and 48 h, and in bone marrow erythrocytes of mice treated orally for seven days with 0.5, 1.0, 2.0, 5.0 and 10.0 mL/kg of flavouring. The results of the plant test showed that grape, plum and orange flavourings, at both exposure times, inhibited cell division and promoted the formation of a significant number of micronuclei and mitotic spindle changes. These alterations were observed in at least one exposure time analysed, demonstrating a significant cytotoxic, genotoxic and mutagenic activity. In mouse bioassay, animals treated with 2.0, 5.0 and 10.0 mL/kg of flavouring died before the seventh day of treatment. The amounts of 0.5 and 1.0 mL/kg of the three additives were cytotoxic to erythrocytes, and treatment with the grape flavouring significantly induced the formation of micronucleated cells in the bone marrow of animals. Therefore, under the study conditions, the grape, plum and orange flavouring additives promoted significant toxicity to cells of the test systems used.

Cytotoxicity of erythrosine (E-127), brilliant blue (E-133) and red 40 (E-129) food dyes in a plant test system - doi: 10.4025/actascibiolsci.v35i4.18419

The objective of this work was to evaluate the cytotoxic effect of the food dyes erythrosine, brilliant blue and red 40 on the cell cycle of Allium cepa L. Each dye was evaluated at doses of 0.4 and 4.0 ml, at exposure times of 24 and 48 hours, in onion root tip cells. Cells and the presence of chromosomal aberrations were analyzed throughout the whole cell cycle, totaling 5,000 cells for each group of bulbs. The mitotic index was calculated and the statistical analysis was conducted through the Chi-square test (p 0.05). From the obtained results, it was verified that the food additives erythrosine and brilliant blue were not cytotoxic to the cells of the test system. However, the red 40 dye, at the two evaluated doses and the two exposure times used in this bioassay have promoted a significant reduction in cell division and induced the emergence of anaphasic and telophasic bridge aberrations and micronucleated cells. Additional cytotoxicity studies should be conducted to add information to these and other previously obtained results in order to evaluate, with property, the action of these three dyes on a cellular level.