ObjectivesThis study investigated the antidepressant and antinociceptive effects of ethanolic extract (SLEE) and pure fruticuline A obtained from Salvia lachnostachys leaves on rats and mice.MethodsIn this study, SLEE (100 mg/kg, p.o. route) was evaluated for its effects on spared nerve injury (SNI) in rats. The animals were submitted to mechanical sensitivity, forced swim (FST) and cold sensitivity tests 10 and 15 days after surgery. SLEE (100 mg/kg, p.o.) and fruticuline A (3 mg/kg, p.o.) were also evaluated with respect to nociceptive behavior induced by formalin. In addition, clonidine-induced depressive-like behavior was also analyzed.ResultsThe oral administration of SLEE for up to 15 days and the subcutaneous injection of 10 mg/kg of ketamine (positive control) significantly inhibited SNI-induced mechanical hyperalgesia and decreased immobility in the FST. On the 15th day of oral treatment, SLEE prevented the SNI-induced increase in cold sensitivity. In the formalin test, SLEE and fruticuline A significantly reduced the frequency of paw licking during the first and second phases and decreased the formation of edema. In locomotor analysis (open field test without clonidine treatment), SLEE and fruticuline A did not alter the response. SLEE and fruticuline A significantly attenuated clonidine-induced suppression of spontaneous locomotor activity (squares invaded and licking) and emotionality (grooming and freezing) compared with controls, similar to the naive group.ConclusionSLEE exhibits antihyperalgesic, antidepressant, and antinociceptive effects, and fruticuline A appears to be at least partly responsible for the effects of SLEE. Together, these results demonstrate the antidepressive effects of SLEE and fruticuline A and indicate that both derivatives obtained from S. lachnostachys act against spontaneous neuropathic pain.
Natural products have been recognized as important bioactive compounds on the basis of their wide biological properties. Here we investigated the antitumor effect and molecular mechanisms of the diterpene Fruticuline A (fruti) from Salvia lachnostachys, in human cancer cell lineages and Solid Ehrlich Carcinoma in mice. Fruti reduced MCF-7 and HepG2 proliferation by the reduction of Cyclin D1 levels and decreased NF-κB gene levels in both cell types. Furthermore, fruti also induced apoptosis in HepG2 cells, reduced Bcl-2 gene expression and induced necroptosis by increasing Ripk in MCF-7 cells. In mice, fruti prevented tumor development and reduced Cyclin D1, Bcl-2 and Rela gene levels, and reduced the p-NF-κB/NF-κB ratio in tumor tissue. Furthermore, fruti induced necrosis and apoptosis, increased N-acetyl-β-D-glucosaminidase and TNF-α levels and reduced IL-10 and Vegf levels in tumor tissue. Collectively, fruti exerts antitumor effects through the inhibition of the NF-κB pathway, reducing Cyclin D1 and Bcl-2 levels. In vitro the apoptosis and necroptosis pathways are involved in the cellular death, whereas in vivo, cells undergo necrosis by increased tumor inflammation and reduction of angiogenesis. Thus, fruticuline A acts in tumor cells by multiple mechanisms and represents a promising molecule for drug development in cancer treatment.
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