Sterculic Acid Alters Adhesion Molecules Expression and Extracellular Matrix Compounds to Regulate Migration of Lung Cancer Cells

Sterculic acid (SA) is a cyclopropenoid fatty acid isolated from Sterculia foetida seeds. This molecule is a well-known inhibitor of SCD1 enzyme, also known as ∆9-desaturase, which main function is related to lipid metabolism. However, recent studies have demonstrated that it also modifies many other pathways and the underlying gene expression. SCD overexpression, or up-regulated activity, has been associated with tumor aggressiveness and poor prognosis in many cancer types. Scd1 down-regulation, with different inhibitors or molecular strategies, reduces tumor cell survival and cell proliferation, as well as the chemoresistance associated with cancer stem cell presence. However, SA effects over cancer cell migration and extracellular matrix or adhesion molecules have not been described in cancer cells up to now. We used different migration assays and qPCR gene expression analysis to evaluate the effects of SA treatment in cancer cells. The results reveal that SA induces tumoral cell death at high doses, but we also observed that lower SA-treatments induce cell adhesion-migration capacity reduction as a result of modifications in the expression of genes related to integrins and extracellular matrix compounds. Overall, the functional and transcriptomic findings suggest that SA could represent a new inhibitor activity of epithelial to mesenchymal transition.

Anopheles coluzzii stearoyl-CoA desaturase is essential for adult female survival and reproduction upon blood feeding

Vitellogenesis and oocyte maturation require anautogenous female Anopheles mosquitoes to obtain a bloodmeal from a vertebrate host. The bloodmeal is rich in proteins that are readily broken down into amino acids in the midgut lumen and absorbed by the midgut epithelial cells where they are converted into lipids and then transported to other tissues including ovaries. The stearoyl-CoA desaturase (SCD) plays a pivotal role in this process by converting saturated (SFAs) to unsaturated (UFAs) fatty acids; the latter being essential for maintaining cell membrane fluidity amongst other housekeeping functions. Here, we report the functional and phenotypic characterization of SCD1 in the malaria vector mosquito Anopheles coluzzii. We show that RNA interference (RNAi) silencing of SCD1 and administration of sterculic acid (SA), a small molecule inhibitor of SCD1, significantly impact on the survival and reproduction of female mosquitoes following blood feeding. Microscopic observations reveal that the mosquito thorax is quickly filled with blood, a phenomenon likely caused by the collapse of midgut epithelial cell membranes, and that epithelial cells are depleted of lipid droplets and oocytes fail to mature. Transcriptional profiling shows that genes involved in protein, lipid and carbohydrate metabolism and immunity-related genes are the most affected by SCD1 knock down (KD) in blood-fed mosquitoes. Metabolic profiling reveals that these mosquitoes exhibit increased amounts of saturated fatty acids and TCA cycle intermediates, highlighting the biochemical framework by which the SCD1 KD phenotype manifests as a result of a detrimental metabolic syndrome. Accumulation of SFAs is also the likely cause of the potent immune response observed in the absence of infection, which resembles an auto-inflammatory condition. These data provide insights into mosquito bloodmeal metabolism and lipid homeostasis and could inform efforts to develop novel interventions against mosquito-borne diseases.

Determination of Cyclopropenoid Fatty Acids in Ewe Milk Fat by GC-MS after Intravenous Administration of Sterculic Acid

Cyclopropenoid fatty acids (CPEFA), found in oilseeds from Malvaceae and Sterculiaceae, have been shown to interfere with the endogenous synthesis of several bioactive lipids of dairy fat, such as cis-9, trans-11 18:2 and cis-9 18:1, by inhibiting Δ9-desaturase. No previous study has reported the presence of sterculic acid in animal fat and its incorporation in tissues after its administration, due to the lack of a proper methodology. In the present research, a GC-MS method based on cold base derivatization to fatty acids methylesters was developed to determine CPEFA in ewe milk triglycerides, after infusing sterculic acid (0.5 g/day) to six lactating ewes. An alternative derivatization based on silanyzation followed by GC-MS analysis was also tested, showing its possible applicability when CPEFA are present in the form of free fatty acids. Sterculic acid was detected in ewe milk triglycerides, demonstrating its incorporation from the bloodstream into milk by the mammary gland. The mean transfer rate represented 8.0 ± 1.0% of the daily dose. This study provides, for the first time, the presence of sterculic acid in milk fat, supporting the importance of understanding its occurrence in vivo and encouraging further research to determine whether it can be present in foods, such as dairy products, obtained under practical farming conditions.

Anopheles coluzzii stearoyl-CoA desaturase is essential for adult female survival and reproduction upon blood feeding

Vitellogenesis and oocyte maturation require anautogenous female Anopheles mosquitoes to obtain a bloodmeal from a vertebrate host. The bloodmeal is rich in proteins that are readily broken down into amino acids in the midgut lumen and absorbed by the midgut epithelial cells where they are converted into lipids and then transported to other tissues including ovaries. The stearoyl-CoA desaturase (SCD) plays a pivotal role in this process by converting saturated (SFAs) to unsaturated (UFAs) fatty acids; the latter being essential for maintaining cell membrane fluidity amongst other housekeeping functions. Here, we report the functional and phenotypic characterization of SCD1 in the malaria vector mosquito Anopheles coluzzii. We show that RNA interference (RNAi) silencing of SCD1 and administration of sterculic acid (SA), a small molecule inhibitor of SCD1, significantly impact on the survival and reproduction of female mosquitoes following blood feeding. Microscopic observations reveal that the mosquito thorax is quickly filled with blood, a phenomenon likely caused by the collapse of midgut epithelial cell membranes, and that epithelial cells are depleted of lipid droplets and oocytes fail to mature. Transcriptional profiling shows that genes involved in protein, lipid and carbohydrate metabolism and immunity-related genes are the most affected by SCD1 knock down (KD) in blood-fed mosquitoes. Metabolic profiling reveals that these mosquitoes exhibit increased amounts of saturated fatty acids and TCA cycle intermediates, highlighting the biochemical framework by which the SCD1 KD phenotype manifests as a result of a detrimental metabolic syndrome. Accumulation of SFAs is also the likely cause of the potent immune response observed in the absence of infection, which resembles an auto-inflammatory condition. These data provide insights into mosquito bloodmeal metabolism and lipid homeostasis and could inform efforts to develop novel interventions against mosquito-borne diseases.

Genome-Wide Transcriptomic Analysis Identifies Pathways Regulated by Sterculic Acid in Retinal Pigmented Epithelium Cells

In addition to its predominant role in lipid metabolism and body weight control, SCD1 has emerged recently as a potential new target for the treatment of various diseases. Sterculic acid (SA) is a cyclopropene fatty acid with numerous biological activities, generally attributed to its Stearoyl-CoA desaturase (SCD) inhibitory properties. Additional effects exerted by SA, independently of SCD inhibition, may be mediating anti-inflammatory and protective roles in retinal diseases such as age-related macular degeneration (AMD), but the mechanisms involved are poorly understood. In order to provide insights into those mechanisms, genome-wide transcriptomic analyses were carried out in mRPE cells exposed to SA for 24 h. Integrative functional enrichment analysis of genome-wide expression data provided biological insight about the protective mechanisms induced by SA. On the one hand, pivotal genes related to fatty acid biosynthesis, steroid biosynthesis, cell death, actin-cytoskeleton reorganization and extracellular matrix-receptor interaction were significantly downregulated by exposition to SA. On the other hand, genes related to fatty acid degradation and beta-oxidation were significantly upregulated. In conclusion, SA administration to RPE cells regulates crucial pathways related to cell proliferation, inflammation and cell death that may be of interest for the treatment of ocular diseases.

Phytochemical Composition and Pharmacological Effects of Cassia Fistula

Cassia fistula is widely utilized in conventional medicines against various diseases. The plant possesses diverse pharmacological characteristics including anti-tussive, hepatoprotective, anti-pyretic, anti-oxidant, anti-inflammatory, anti-cancer, anti-fungal, anti-microbial, anti-itching, anti-ulcer, anti-epileptic, anti-fertility and wound healing characteristics. Its leaves and bark are used to treat skin diseases,while its roots are useful as diuretic and are used to treat tubercular glands, cardiac disorders, and ulcer. Its fruit pulp is used as a mild laxative in numerous stomach problems. Its flowers are used to treat leprosy, abdominal problems and fever and its seeds possess anti-pyretic, cooling and laxativeproperties. The plant isan important source of tannins, glycosides and flavonoides, linoleic, oleic, stearic and carbohydrates. Its leaves contain glycosides, free rhein, sennosides A and B, isofavoneoxalic acidsandoxyanthraquinones derivatives,while the stem bark contains lepeol, hexacosanol, tannins and B-sitosterol. The pulp is composed of carbohydrate, arginine, protein, leucine and flavonid-3-ol-subordinates. Its pods contain astringent matter, fistulic acids, glutten matter and kaempferol,whereas its seeds are rich in malvalic acid, sterculic acid and vernolic oil. Moreover, aurantimide, ceryl alcohol, kaempferol, anthraquinonees, bianthroquonones and glycosides basic oils are present in the flower.

Ceiba speciosa (A. St.-Hil.) Seeds Oil: Fatty Acids Profiling by GC-MS and NMR and Bioactivity

This study aimed to evaluate the chemical composition by gas chromatography-mass spectrometry (GC-MS) and Nuclear Magnetic Resonance (NMR) analyses, the antioxidant activities evaluated by different in vitro assays namely 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), Ferric Reducing Ability Power (FRAP), and β-carotene bleaching tests, and the inhibitory effects of enzymes linked to obesity (lipase, α-amylase, and α-glucosidase) of fixed seed oil of Ceiba speciosa (A. St.-Hil.). Fourteen compounds were identified. Linoleic acid (28.22%) was the most abundant followed by palmitic acid (19.56%). Malvalic acid (16.15%), sterculic acid (11.11%), and dihydrosterculic acid (2.74%) were also detected. C. speciosa fixed oil exerted a promising ABTS radicals scavenging activity with an IC50 value of 10.21 µg/mL, whereas an IC50 of 77.44 µg/mL against DPPH+ radicals was found. C. speciosa fixed oil inhibited lipase with an IC50 value of 127.57 µg/mL. The present investigation confirmed the functional properties of C. speciosa fixed oil, and proposes its use as valuable source of bioactive constituents.

Sterculic Acid: The Mechanisms of Action beyond Stearoyl-CoA Desaturase Inhibition and Therapeutic Opportunities in Human Diseases

In many tissues, stearoyl-CoA desaturase 1 (SCD1) catalyzes the biosynthesis of monounsaturated fatty acids (MUFAS), (i.e., palmitoleate and oleate) from their saturated fatty acid (SFA) precursors (i.e., palmitate and stearate), influencing cellular membrane physiology and signaling, leading to broad effects on human physiology. In addition to its predominant role in lipid metabolism and body weight control, SCD1 has emerged recently as a potential new target for the treatment for various diseases, such as nonalcoholic steatohepatitis, Alzheimer’s disease, cancer, and skin disorders. Sterculic acid (SA) is a cyclopropene fatty acid originally found in the seeds of the plant Sterculia foetida with numerous biological activities. On the one hand, its ability to inhibit stearoyl-CoA desaturase (SCD) allows its use as a coadjuvant of several pathologies where this enzyme has been associated. On the other hand, additional effects independently of its SCD inhibitory properties, involve anti-inflammatory and protective roles in retinal diseases such as age-related macular degeneration (AMD). This review aims to summarize the mechanisms by which SA exerts its actions and to highlight the emerging areas where this natural compound may be of help for the development of new therapies for human diseases.

Pembuatan asam lemak bercabang dari minyak kepoh

Oil from kepoh tree (Sterculiafoetida L.) seed kernel is a unique oil because it contains fatty acid which has a cyclopropenoid groups and has almost 90% of composition of the oil. The acid is called sterculic acid which has molecular formula C19H34O2. The fatty acids and derivates has an advance characteristic when it is used as cosmetics, lubricants, paint and plastic products. Its branched alcohol ester is expected as an additives for pour point depressant in fuel or lubricant. In this research, the sterculic acid has possibility to be converted to branched fatty acid methyl ester that is 10-methyl octadecanoic methyl ester through rearrangement of cyclopropenoid group and continued by hydrogenation of its double bond with Palladium catalyst. The product characteristic is reported in each stage of processes in term of iodine number and saponification number. After hydrogenation for 5 hours, it's founded that iodine value for methyl ester is reduced until 2,84 and its saponification value increased up to 476.08. This is shown that saturated branched methyl ester has been formed.Keywords: Sterculia foetida L.kepoh oil, Branched Fatty Acid, Cyclopropenoid Group, Methanolysis, Biodiesel AbstrakMinyak dari inti biji buah pohon kepoh (Sterculiafoetida L.) tergolong minyak nabati yang unik karena komponen utama asam lemaknya adalah asam sterkulat yang berumus molekul C19H34O2 dengan rantai karbonnya mempunyai gugus cyclopropenoid. Asam sterkulat dapat dikonversi menjadi asam lemak bercabang yaitu asam 10-metil oktadekanoat C19H34O2. Asam-asam lemak ini atau turunannya dapat digunakan sebagai komponen racikan/ramuan yang melahirkan karakteristik unggul pada berbagai produk seperti kosmetik, pelumas, cat, dan plastik. Ester isopropilnya diharapkan dapat digunakan sebagai bubuhan (additive), penurun titik tuang (pour point depressant) pada pelumas dan biodiesel. Pada penelitian ini, ditunjukkan bahwa asam sterkulat dalam minyak kepoh dapat dikonversi menjadi asam lemak bercabang yaitu 10-metil oktadekanoat dalam bentuk ester metilnya yang bercampur dengan ester metil lainnya, melalui rute metanolisis (transesterifikasi dengan metanol) minyak kepoh, dilanjutkan penyusunan ulang gugus siklopropenoid dan hidrogenasi ikatan-ikatan rangkap dengan katalis Palladium. Setelah hidrogenasi selama 5jam ditemukan bahwa bahwa angka iodium ester metil sudah tereduksi sampai 2,84 dan angka penyabunan meningkat sampai 476,08. Hal ini menunjukkan bahwa telah terbentuk ester metil bercabang yang jenuh, yaitu 9-metil metilheptadekanoat dan 10-metil metioktadekanoat.Kata Kunci: Sterculia foetida L. kepoh oil, Branched Fatty Acid, Cyclopropenoid Group, Methanolysis, Biodiesel

Enzymatic production of sterculic acid from the novel Phoenix tree seed oil: Optimization and kinetic study

Phoenix tree (Firmiana simplex) seed oil is a novel oil which is rich in sterculic acid. Sterculic acid, a cyclopropene fatty acid, can be used as the inhibitor of the stearoyl-CoA desaturase system and mammary carcinomas growth. In this work, Lipozyme TLIM-catalyzed hydrolysis of the novel Phoenix tree seed oil was used to prepare sterculic acid. High temperature GC-FID and the degree of hydrolysis (DH) were used to monitor the reaction progress. Effects of reaction variables on the hydrolysis were evaluated and optimized using response surface methodology. Results showed that sterculic acid can be successfully prepared from the novel seed oil, and the effect of reaction variables on the hydrolysis decreased in the order of reaction time > enzyme load > temperature. A high yield of fatty acids (DH, 98.2±0.8%) can be obtained under optimized conditions (45 ºC, mass ratio of water to oil 10:1, enzyme load 10%, and 18 h). The Arrhenius equation for the hydrolysis was LnV0 = 9.12-4721/T. The activation energy was 39.25KJ/mol. The kinetic values for Vmax, K/m were 0.232mol/(L∙min) and 0.084 mol/L, respectively.