Anti-inflammatory activity of argan oil and its minor components.

Argan oil is thought to be the most expensive edible oil worldwide. It is difficult to produce and the argan tree only grows in a limited geographical area, notably Morocco and Algeria. Because it is produced by mechanical means, argan oil contains "minor" components that might be endowed with healthful effects. We investigated in vivo the anti-inflammatory activities of argan oil and its unsaponifiable fraction, using diclofenac as the control, in a carrageenan-induced rat model of inflammation. Rats were given different amounts of argan oil or its unsaponifiable fraction, by gavage. We report that argan oil and its "minor" components effectively lessen the inflammatory actions of carrageenan. Far from being "pharmacological" the actions of argan oil are comparable with those of diclofenac in the short, i.e. 4 h term. Sustained consumption of argan oil might, therefore, contribute to lessen the burden of degenerative diseases associated with higher inflammatory status.

Effects of polyphenols and lipids from Pennisetum glaucum grains on T-cell activation: modulation of Ca(2+) and ERK1/ERK2 signaling.

BACKGROUND: Pearl millet (PM), i.e., Pennisetum glaucum, is widely grown in Africa and known for its anti-oxidant and anti-hyperlipidemic properties. METHODS: The P. glaucum grains were obtained from the region of Ouled Aïssa (South of Algeria). We assessed the effects of phenolic compounds and lipids, extracted from seeds of P. glaucum, on rat lymphocyte proliferation, activated by phorbol 12-myristate 13-acetate and ionomycin. In order to explore signaling pathway, triggered by these compounds, we assessed interleukin-2 (IL-2) mRNA expression and extracellular signal-regulated kinase-1/2 (ERK1/ERK2) phosphorylation. Finally, we determined increases in free intracellular Ca(2+) concentrations, [Ca(2+)]i, by employing Fura-2/AM in rat lymphocytes. RESULTS: The composition of P. glaucum grains in polyphenols was estimated to be 1660 µg gallic acid equivalents (GAE)/g. Lipids represented 4.5 %, and more than 72% of the fatty acids belonged to unsaturated family. Our investigation showed that both lipid and phenolic compounds inhibited mitogen-induced T-cell proliferation. Compared with phenolic compounds, lipids exerted weaker effects on ERK-1/ERK2 phosphorylation and Ca(2+) signaling in mitogen-activated T-cells. CONCLUSION: We conclude that the immunomodulatory effects of P. glaucum could be contributed by its phenolic and lipid contents.

Argan oil improves surrogate markers of CVD in humans.

Limited - though increasing - evidence suggests that argan oil might be endowed with potential healthful properties, mostly in the areas of CVD and prostate cancer. We sought to comprehensively determine the effects of argan oil supplementation on the plasma lipid profile and antioxidant status of a group of healthy Algerian subjects, compared with matched controls. A total of twenty healthy subjects consumed 15 g/d of argan oil - with toasted bread - for breakfast, during 4 weeks (intervention group), whereas twenty matched controls followed their habitual diet, but did not consume argan oil. The study lasted 30 d. At the end of the study, argan oil-supplemented subjects exhibited higher plasma vitamin E concentrations, lower total and LDL-cholesterol, lower TAG and improved plasma and cellular antioxidant profile, when compared with controls. In conclusion, we showed that Algerian argan oil is able to positively modulate some surrogate markers of CVD, through mechanisms which warrant further investigation.

Zizyphus lotus L. fruit attenuates obesity-associated alterations: in vivo mechanisms.

CONTEXT: Zizyphus lotus L., ZL is a Mediterranean plant and widely consumed for its beneficial medicinal properties. Objective: We assessed the effects of ZL fruit on diet-induced obesity. Materials and methods: Male C57BL/6j mice were divided into three groups. Each group received either a standard diet or a high-fat diet, HFD (30% of palm oil, w/v) or a HFD-supplemented with ZL fruit powder (10%, w/w) for six weeks, followed by a six weeks period, in which animals were maintained on the HFD and ZL aqueous extract (1%, w/v). We measured plasma parameters and assessed the expression of key genes involved in energy metabolism and inflammation. Results: ZL fruit improved glycaemia, lipids concentrations and inflammation in obese mice. Discussion and conclusion: Our investigations showed that ZL fruit improved glucose tolerance, dyslipidaemia and fatty liver disease, but not the severity of HFD-induced obesity in mice.

Zizyphus lotus L. (Desf.) modulates antioxidant activity and human T-cell proliferation.

BACKGROUND: Zizyphus lotus L. (Desf.) also known as Jujube, is a deciduous shrub which belongs to Rhamnaceae family. This plant is used in Algerian traditional medicine for its anti-diabetic, sedative, analgesic, anti-inflammatory and hypoglycaemic activities. In the present study, we determined the concentrations of different vitamins (vitamin A, C and E) and fatty acids in root, stem, leaves, fruit pulp and seed of Zizyphus lotus L. (Desf.) and assessed the effects of their aqueous extracts on antioxidant status and human T-cell proliferation. METHODS: Aqueous filtrates from different parts, i.e, root, leaf, stem, fruit pulp and seed, of Zizyphus lotus L. (Desf.) were prepared. Vitamin C levels were determined by precipitating with 10% trichloroacetic acid and vitamin A and E were assessed by HPLC. Lipid composition of these extracts was determined by gas-liquid chromatography. Anti-oxidant capacity was evaluated by using anti-radical resistance kit [Kit Radicaux Libres (KRL@; Kirial International SA, Couternon, France)]. T-cell blastogenesis was assessed by the incorporation of 3H-thymidine. IL-2 gene expression was evaluated by RT-qPCR. RESULTS: Our results show that fruit pulp contained higher vitamin A and C contents than other parts of the plant. Furthermore, the fruit pulp was the richest source of linoleic acid (18:2n-6), a precursor of n-6 fatty acids. Fruit seeds possessed higher vitamin C levels than leaves, roots and stem. The leaves were the richest source of vitamin E and linolenic acid (18:3n-3), a precursor of n-3 fatty acids. The antioxidant capacity of the different extracts, measured by KRL@ test, was as follows: pulp < seed < leaf < root < stem. As far as T-cell proliferation is concerned, we observed that the different extracts of Zizyphus lotus L. (Desf.) exerted immunosuppressive effects. CONCLUSION: Seed extracts exerted the most potent immunosuppressive effects on T cell proliferation and IL-2 mRNA expression. The results of the present study are discussed in the light of their use to modulate the immune-mediated diseases.

Bioactive compounds and antioxidant activity of Rhaponticum acaule (L.) DC.

Rhaponticum acaule (L.) DC. is a medicinal plant commonly used for the treatment of some illnesses such as gastrointestinal infections. In this work, we report the composition of different parts of this plant on phenolic compounds, their quantification, and antioxidant activity. The obtained results reported that methanolic extracts of the three parts studied revealed high phenolic contents. For flavonoid contents, the highest contents were reported in organic extracts of leaf part. In addition, results obtained from the study of the antioxidant activity showed that methanolic extract of root presented the highest activity, in DPPH• scavenging ability test with an IC50 of 0.31 ± 0.04 mg/mL and in FRAP test with an EC50 of 1.06 ± 0.02 mg/mL. The RP-HPLC-PDA analysis revealed the presence of five phenolic acids (sinapic, caffeic, chlorogenic, ferulic and syringic acids), one flavanone (naringenin), one flavonol (rutin) and vanillin.

Oleanolic acid improves diet-induced obesity by modulating fat preference and inflammation in mice.

Obesity, triggered by high-fat diet (HFD), is associated to altered gustatory perception of dietary lipids. Oleanolic acid (OLA), a triterpene, has been reported to exert anti-obesity effects in animal models. Hence, we investigated the role of OLA in the modulation of oro-sensory perception of lipids in control and HFD-induced obese mice. As expected, OLA-treated obese mice exhibited a decrease in body, liver, and visceral adipose tissue weights. OLA treatment improved glucose tolerance, insulin level, plasma lipopolysaccharide (LPS), and hepatic cholesterol and triglyceride concentrations. OLA-treated obese mice exhibited higher fat preference compared to untreated obese mice, probably due to the increase in mRNA encoding CD36, a fat taste receptor, in mouse taste bud cells (mTBC). This phenomenon was associated with fatty-acid induced increases in free intracellular calcium concentrations, [Ca2+]i, induced in mTBC from OLA-treated obese mice. OLA also influenced the expression of mRNA encoding pro-inflammatory cytokines (IL-1ß and IL-6) and some lipogenic genes (PPARα, SREBP1, FAS, ChREBP, and G6Pase) in liver and adipose tissue. These findings reveal that OLA improves gustatory perception of lipids and exerts protective effects in obesity.

Protective effects of polyphenol-rich infusions from carob (Ceratonia siliqua) leaves and cladodes of Opuntia ficus-indica against inflammation associated with diet-induced obesity and DSS-induced colitis in Swiss mice.

In the present study, we have investigated the effects of polyphenol-rich infusions from carob leaves and OFI-cladodes on inflammation associated with obesity and dextran sulfate sodium (DSS)-induced ulcerative colitis in Swiss mice. In vitro studies revealed that aqueous extracts of carob leaves and OFI-cladodes exhibited anti-inflammatory properties marked by the inhibition of IL-6, TNF-α and nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells concomitant with NF-κß nucleus translocation inhibition. For in vivo investigations, Swiss male mice were subjected to control or high fat diet (HFD). At the 8th week after the start of study, animals received or not 1% infusion of either carob leaves or OFI-cladode for 4 weeks and were subjected to 2% DSS administration in drinking water over last 7 days. After sacrifice, pro-inflammatory cytokines levels in plasma and their mRNA expression in different organs were determined. Results showed that carob leaf and OFI-cladode infusions reduced inflammation severity associated with HFD-induced obesity and DSS-induced acute colitis indicated by decrease in pro-inflammatory cytokines expression (as such TNF-α, IL1b and IL-6) in colon, adipose tissue and spleen. In addition, plasma levels of IL-6 and TNF-α were also curtailed in response to infusions treatment. Thus, carob leaf and OFI-cladode infusions prevented intestinal permeability through the restoration of tight junction proteins (Zo1, occludins) and immune homeostasis. Hence, the anti-inflammatory effect of carob leaves and OFI-cladodes could be attributed to their polyphenols which might alleviate inflammation severity associated with obesity and colitis.

Zizyphin modulates calcium signalling in human taste bud cells and fat taste perception in the mouse.

Zizyphin, isolated from Zizyphus sps. leaf extracts, has been shown to modulate sugar taste perception, and the palatability of a sweet solution is increased by the addition of fatty acids. We, therefore, studied whether zizyphin also modulates fat taste perception. Zizyphin was purified from edible fruit of Zizyphus lotus L. Zizyphin-induced increases in [Ca2+ ]i in human taste bud cells (hTBC). Zizyphin shared the endoplasmic reticulum Ca2+ pool and also recruited, in part, Ca2+ from extracellular environment via the opening of store-operated Ca2+ channels. Zizyphin exerted additive actions on linoleic acid (LA)-induced increases in [Ca2+ ]i in these cells, indicating that zizyphin does not exert its action via fatty acid receptors. However, zizyphin seemed to exert, at least in part, its action via bile acid receptor Takeda-G-protein-receptor-5 in hTBC. In behavioural tests, mice exhibited preference for both LA and zizyphin. Interestingly, zizyphin increased the preference for a solution containing-LA. This study is the first evidence of the modulation of fat taste perception by zizyphin at the cellular level in hTBC. Our study might be helpful for considering the synthesis of zizyphin analogues as 'taste modifiers' with a potential in the management of obesity and lipid-mediated disorders.

Phenolic extract from oleaster (Olea europaea var. Sylvestris) leaves reduces colon cancer growth and induces caspase-dependent apoptosis in colon cancer cells via the mitochondrial apoptotic pathway.

Dietary polyphenols, derived from natural products, have received a great interest for their chemopreventive properties against cancer. In this study, we investigated the effects of phenolic extract of the oleaster leaves (PEOL) on tumor growth in mouse model and on cell death in colon cancer cell lines. We assessed the effect of oleaster leaf infusion on HCT116 (human colon cancer cell line) xenograft growth in athymic nude mice. We observed that oleaster leaf polyphenol-rich infusion limited HCT116 tumor growth in vivo. Investigations of PEOL on two human CRC cell lines showed that PEOL induced apoptosis in HCT116 and HCT8 cells. We demonstrated an activation of caspase-3, -7 and -9 by PEOL and that pre-treatment with the pan-caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk), prevented PEOL-induced cell death. We observed an involvement of the mitochondrial pathway in PEOL-induced apoptosis evidenced by reactive oxygen species (ROS) production, a decrease of mitochondrial membrane potential, and cytochrome c release. Increase in intracellular Ca2+ concentration induced by PEOL represents the early event involved in mitochondrial dysfunction, ROS-induced endoplasmic reticulum (ER) stress and apoptosis induced by PEOL, as ruthenium red, an inhibitor of mitochondrial calcium uptake inhibited apoptotic effect of PEOL, BAPTA/AM inhibited PEOL-induced ROS generation and finally, N-acetyl-L-cysteine reversed ER stress and apoptotic effect of PEOL. These results demonstrate that polyphenols from oleaster leaves might have a strong potential as chemopreventive agent in colorectal cancer.

Correction: Phenolic extract from oleaster (Olea europaea var. Sylvestris) leaves reduces colon cancer growth and induces caspase-dependent apoptosis in colon cancer cells via the mitochondrial apoptotic pathway.

[This corrects the article DOI: 10.1371/journal.pone.0170823.].

Oleaster oil positively modulates plasma lipids in humans.

The olive tree had been domesticated during the early Neolithic in the Near East, and more than 1000 different cultivars have been identified to date. However, examples of wild olive trees (Olea europaea oleaster) can still be found in the Mediterranean basin. Evidence of oleaster use for oil production can be found in historical and sacred texts, such as the Odyssey, the Holey Koran, and the Holey Bible. While the nutritional and healthful properties of olive oil are actively being explored, there are no data on the human actions of oleaster oil. Therefore, we investigated the effect of prolonged, i.e., 1 month, consumption of oleaster oil on the lipid profile of a 40 healthy Algerian subjects (aged 27.9 ± 3.85 years), as compared to nonconsumers from the same area. Plasma urea, creatinine, and uric acid concentrations and glycemia did not significantly differ, at the end of the study, between controls and oleaster-oil-supplemented subjects. Conversely, we recorded significant decreases of plasma triglyceride concentration (-24.8%; p < 0.05), total cholesterol (-12.13%; p < 0.05), and low-density lipoprotein-cholesterol (LDL-C) (-24.39%; p < 0.05) in oleaster-oil-treated subjects. Concomitantly, high-density lipoprotein-cholesterol (HDL-C) concentrations were significantly increased (17.94%; p < 0.05) by oleaster oil administration. In conclusion, we show that oil obtained from feral olive trees, i.e., oleasters, improves the plasma lipid profile of healthy volunteers.