Capsaicin intake and oral carcinogenesis: A systematic review / Ingesta de capsaicina y carcinogénesis oral: una revisión sistemática

Background: Chili is the most heavily and frequently consumed spice, either as a flavouring or colouring agent,and it is also a major source of pro-vitamin A, vitamin E and C. The main capsaicinoid found in chili peppers iscapsaicin. It has been demonstrated that capsaicin acts as a cancer-suppressing agent through its antioxidant andanti-inflammatory effects, by blocking several signal transduction pathways. Oral squamous cell carcinoma isone of the most prevalent cancer worldwide. It is noteworthy that in countries where populations of diverse ethnicgroups co-exist, differences have been observed in terms of incidence of oral cancer. The variances in their dietcould explain, at least in part, these differences. The objective of this systematic review is to explore if there isevidence of a possible relationship between capsaicin intake and the incidence of oral squamous cell carcinoma,and discuss such association.Material and Methods: A bibliographical search was made in PubMed, Scopus and Web of Science databases, andfinally 7 experimental studies were included; OHAT risk of bias tool was used to assess their quality.Results: All the studies confirm that capsaicin is a chemopreventive agent that prevents the development of oralcancer, through inhibition of malignant cell proliferation and increase of apoptosis.Conclusions: More human studies are needed in order to clarify the real link between consumption of chili (cap-saicin) and the prevalence of oral cancer.(AU)

Author Correction: Hesperidin and capsaicin, but not the combination, prevent hepatic steatosis and other metabolic syndrome-related alterations in western diet-fed rats.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Relationship between Changes in Microbiota and Liver Steatosis Induced by High-Fat Feeding-A Review of Rodent Models.

Several studies have observed that gut microbiota can play a critical role in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) development. The gut microbiota is influenced by different environmental factors, which include diet. The aim of the present review is to summarize the information provided in the literature concerning the impact of changes in gut microbiota on the effects which dietary fat has on liver steatosis in rodent models. Most studies in which high-fat feeding has induced steatosis have reported reduced microbiota diversity, regardless of the percentage of energy provided by fat. At the phylum level, an increase in Firmicutes and a reduction in Bacteroidetes is commonly found, although widely diverging results have been described at class, order, family, and genus levels, likely due to differences in experimental design. Unfortunately, this fact makes it difficult to reach clear conclusions concerning the specific microbiota patterns associated with this feeding pattern. With regard to the relationship between high-fat feeding-induced changes in liver and microbiota composition, although several mechanisms such as alteration of gut integrity and increased permeability, inflammation, and metabolite production have been proposed, more scientific evidence is needed to address this issue and thus further studies are needed.

Effects of Quercetin Metabolites on Triglyceride Metabolism of 3T3-L1 Preadipocytes and Mature Adipocytes.

Quercetin (Q) has rapid metabolism, which may make it worthwhile to focus on the potential activity of its metabolites. Our aim was to evaluate the triglyceride-lowering effects of Q metabolites in mature and pre-adipocytes, and to compare them to those induced by Q. 3T3-L1 mature and pre-adipocytes were treated with 0.1, 1 and 10 µM of Q, tamarixetin (TAM), isorhamnetin (ISO), quercetin-3-O-glucuronide (3G), quercetin-3-O-sulfate (3S), as well as with 3S and quercetin-4-O-sulfate (4S) mixture (3S+4S). Triglyceride (TG) content in both cell types, as well as free fatty acid (FFA) and glycerol in the incubation medium of mature adipocytes were measured spectrophotometrically. Gene expression was assessed by RT-PCR. In mature adipocytes, Q decreased TG at 1 and 10 µM, 3S metabolite at 1 and 10 µM, and 3S+4S mixture at 10 µM. 3S treatment modified the glucose uptake, and TG assembling, but not lipolysis or apoptosis. During differentiation, only 10 µM of ISO reduced TG content, as did Q at physiological doses. In conclusion, 3S metabolite but not ISO, 3G, 4S and TAM metabolites can contribute to the in vivo delipidating effect of Q.

Hesperidin and capsaicin, but not the combination, prevent hepatic steatosis and other metabolic syndrome-related alterations in western diet-fed rats.

We aimed to assess the potential effects of hesperidin and capsaicin, independently and in combination, to prevent the development of obesity and its related metabolic alterations in rats fed an obesogenic diet. Three-month-old male Wistar rats were divided into 5 groups: Control (animals fed a standard diet), WD (animals fed a high fat/sucrose (western) diet), HESP (animals fed a western diet + hesperidin (100 mg/kg/day)), CAP (animals fed a western diet + capsaicin (4 mg/kg/day)), and HESP + CAP (animals fed a western diet + hesperidin (100 mg/kg/day) + capsaicin (4 mg/kg/day)). Hesperidin and capsaicin were administered by gavage. Capsaicin decreased body fat gain and prevented insulin resistance, whereas hesperidin showed little effect on body fat gain and no apparent effects on insulin resistance. No additive effects were observed with the combination. Capsaicin and hesperidin, separately, improved blood lipid profile, diminished hepatic lipid accumulation, and prevented non-alcoholic steatohepatitis in western diet-fed rats, but the combination showed lower effects. Hesperidin alone, and to a lesser extent capsaicin or the combination, displayed hypotensive effects in western diet-fed rats. In conclusion, capsaicin and hesperidin, separately, exhibit health beneficial effects on metabolic syndrome-related alterations in western diet-fed rats, but the effects are mitigated with the combination.

Combination of Capsaicin and Hesperidin Reduces the Effectiveness of Each Compound To Decrease the Adipocyte Size and To Induce Browning Features in Adipose Tissue of Western Diet Fed Rats.

We explored the potential of hesperidin and capsaicin, separately and in combination, to induce white adipose tissue (WAT) browning and to help body weight management in Western diet-fed rats. Adult male Wistar rats were fed for 8 weeks with Western diet and treated daily with hesperidin (100 mg/kg/day), capsaicin (4 mg/kg/day), hesperidin (100 mg/kg/day) + capsaicin (4 mg/kg/day), or the vehicle. Hesperidin and capsaicin separately, but not (or to a lesser extent) the combination, resulted in a decreased size of adipocytes and induced emergence of multilocular brown-like adipocytes positive for UCP1 and CIDEA in retroperitoneal WAT. Expression levels of browning markers, such as Prdm16, in inguinal WAT also increased with capsaicin treatment compared with the vehicle (145% ± 17% vs 92% ± 21%, P < 0.05), but no significant effects were found with the combination (106% ± 12%). Thus, the combination of both bioactives reduces the effectiveness of each compound to decrease the adipocyte size and induce WAT browning.

Phenolic compounds apigenin, hesperidin and kaempferol reduce in vitro lipid accumulation in human adipocytes.

BACKGROUND: Adipocytes derived from human mesenchymal stem cells (MSCs) are widely used to investigate adipogenesis. Taking into account both the novelty of these MSCs and the scarcity of studies focused on the effects of phenolic compounds, the aim of the present study was to analyze the effect of apigenin, hesperidin and kaempferol on pre-adipocyte and mature adipocytes derived from this type of cells. In addition, the expression of genes involved in TG accumulation was also measured. METHODS: Pre-adipocytes were cultured from day 0 to day 8 and mature adipocytes for 48 h with the polyphenols at doses of 1, 10 and 25 µM. RESULTS: Apigenin did not show an anti-adipogenic action. Pre-adipocytes treated with hesperidin and kaempferol showed reduced TG content at the three experimental doses. Apigenin did not modify the expression of the main adipogenic genes (c/ebpß, c/ebpα, pparγ and srebp1c), hesperidin inhibited genes involved in the three phases of adipogenesis (c/ebpß, srebp1c and perilipin) and kaempferol reduced c/ebpß. In mature adipocytes, the three polyphenols reduced TG accumulation at the dose of 25 µM, but not at lower doses. All compounds increased mRNA levels of atgl. Apigenin and hesperidin decreased fasn expression. The present study shows the anti-adipogenic effect and delipidating effects of apigenin, hesperidin and kaempferol in human adipocytes derived from hMSCs. While hesperidin blocks all the stages of adipogenesis, kaempferol only inhibits the early stage. Regarding mature adipocytes, the three compounds reduce TG accumulation by activating, at least in part, lipolysis, and in the case of hesperidin and apigenin, also by reducing lipogenesis. CONCLUSIONS: The present study shows for the first time the anti-adipogenic effect and delipidating effect of apigenin, hesperidin and kaempferol in human adipocytes derived from MSCs for the first time.

Screening of potential anti-adipogenic effects of phenolic compounds showing different chemical structure in 3T3-L1 preadipocytes.

This study was designed to analyze the anti-adipogenic effect of fifteen phenolic compounds from various chemical groups in 3T3-L1 pre-adipocytes. Cells were treated with 25 µM, 10 µM or 1 µM of apigenin, luteolin, catechin, epicatechin, epigallocatechin, genistein, daizein, naringenin, hesperidin, quercetin, kaempferol, resveratrol, vanillic acid, piceatannol and pterostilbene for 8 days. At 25 µM lipid accumulation was reduced by all the compounds, with the exception of catechin, epicatechin and epigallocatechin. At a dose of 10 µM apigenin, luteolin, naringenin, hesperidin, quercetin and kaempferol induced significant reductions, and at 1 µM only naringenin, hesperidin and quercetin were effective. The expression of c/ebpα was not. C/ebpß was significantly reduced by genistein and kaempferol, pparγ by genistein and pterostilbene, srebp1c by luteolin, genistein, hesperidin, kaempferol, pterostilbene and vanillic acid, and lpl by kaempferol. In conclusion, the most effective phenolic compounds are naringenin, hesperidin and quercetin. Differences were found in terms of effects on the expression of genes involved in adipogenesis among the analyzed compounds.