Cytotoxic abietane-derivative diterpenoids of Salvia lachnostachys

Oliveira, Cristhian Santos; Salvador, Marcos José; Carvalho, João Ernesto de; Santos, Élide Pereira dos; Barison, Andersson; Stefanello, Maria ÿlida A.

doi:10.1016/j.phytol.2016.07.005

Cited by 13 publications

(13 citation statements)

References 11 publications

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“…Fruti is a diterpene quinone and has some biological properties already described, such as antinociceptive, anti-inflammatory, antidepressive and antimicrobial 12,13,16 . Cytotoxicity of fruti against a range of human cancer cell lines has also been demonstrated, including U251 (glioma, central nervous system), UACC-62 (melanoma), MCF-7 (breast), NCI-ADR/RES (ovarian-resistant), NCI-H460 (lung, non-small-cell), PC-3 (prostate), OVCAR-3 (ovarian) and HT-29 www.nature.com/scientificreports/ (colon) 10 . However, none of these studies investigated the antitumor effect of fruti and its action mechanism.…”

Section: Discussionmentioning

confidence: 99%

Fruticuline A, a chemically-defined diterpene, exerts antineoplastic effects in vitro and in vivo by multiple mechanisms

Corso

Stipp

Radulski

et al. 2020

Sci Rep

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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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Section: Discussionmentioning

confidence: 99%

Fruticuline A, a chemically-defined diterpene, exerts antineoplastic effects in vitro and in vivo by multiple mechanisms

Corso

Stipp

Radulski

et al. 2020

Sci Rep

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“…In the present study, the main findings include the antidepressive and antinociceptive effects of SLEE and pure fruticuline A, which was isolated from SLEE. This compound is a nor -abietane diterpenoid with antimicrobial [ 15 ], anti-inflammatory [ 6 ], and cytotoxic effects against the activity of human cancer cell lines [ 7 ]. The relationship between fruticuline A and SLEE is that crude extracts contain about 3% of this compound and all tests made with fruticuline A followed this proportion leading similar efficacy with both products from S .…”

Section: Discussionmentioning

confidence: 99%

“…Fruticuline A (63 mg) was obtained from fraction 6 (200 mg) after preparative TLC in toluene or benzene:CH 2 Cl 2 8:2. Fruticuline A was identified by NMR analysis and literature comparison [ 7 , 14 , 15 ].…”

Section: Methodsmentioning

confidence: 99%

“…Salvia lachnostachys Benth is an herb that is native to Brazil and whose ethanolic extract from leaves (SLEE) has been studied. Triterpenes and diterpenes, including fruticuline A, were previously isolated from SLEE using chromagraphic techniques and identified by 1 H and 13 C NMR [ 7 ]. SLEE and fruticuline A exhibited anti-inflammatory (paw edema and pleurisy induced by carrageenan injection) and antihyperalgesic inflammatory effects.…”

Section: Introductionmentioning

confidence: 99%

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Antidepressive and antinociceptive effects of ethanolic extract and fruticuline A from Salvia lachnostachys Benth leaves on rodents

et al. 2017

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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.

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“…Terpenes are secondary metabolites that occur across a wide range of plant tissue types and present several biological activities. Some of them have shown remarkable antiviral [ 6 , 7 , 8 ] and cytotoxic effects [ 9 , 10 , 11 ]. In previous works, we prepared series of semisynthetic derivatives of a large number of terpenes in the search for biologically active derivatives [ 12 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Antiviral and Cytotoxic Activity of Novel Terpenyl Hybrid Molecules Prepared by Click Chemistry

et al. 2018

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Naturally occurring terpenes were combined by click reactions to generate sixteen hybrid molecules. The diterpene imbricatolic acid (IA) containing an azide group was used as starting compound for the synthesis of all the derivatives. The alkyne group in the terpenes cyperenoic acid, dehydroabietinol, carnosic acid γ-lactone, ferruginol, oleanolic acid and aleuritolic acid was obtained by esterification using appropriate alcohols or acids. The hybrid compounds were prepared by combining the IA azide function with the different terpene-alkynes under click chemistry conditions. The cytotoxic activity of the terpene hybrids 1–16 was assessed against Vero cells and tumour cell lines (HEP-2, C6 and Raw 264.7). Compounds 1, 2, 3 and 7 showed cytotoxic activity against the tested cell lines. The antiviral activity of the compounds was evaluated against HSV-1 KOS, Field and B2006 strain. For the pairs of hybrid compounds formed between IA-diterpene (compounds 3–8, except for compound 7), a moderate activity was observed against the three HSV-1 strains with an interesting selectivity index (SI ≥10, SI = CC50/CE50) for some compounds.

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Cytotoxic abietane-derivative diterpenoids of Salvia lachnostachys

Cited by 13 publications

References 11 publications

Fruticuline A, a chemically-defined diterpene, exerts antineoplastic effects in vitro and in vivo by multiple mechanisms

Fruticuline A, a chemically-defined diterpene, exerts antineoplastic effects in vitro and in vivo by multiple mechanisms

Antidepressive and antinociceptive effects of ethanolic extract and fruticuline A from Salvia lachnostachys Benth leaves on rodents

Synthesis, Antiviral and Cytotoxic Activity of Novel Terpenyl Hybrid Molecules Prepared by Click Chemistry

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