Gerda Flo

4-demethyl simmondsin from Simmondsia chinensis

Jojoba seed meal (Simmondsia chinensis) contains approximately 15% glucosides identified as simmondsin, 5-demethyl simmondsin, didemethyl simmondsin, along with simmondsin 2%-ferulate, 4-demethyl simmondsin 2%-ferulate, and 5-demethyl simmondsin ferulate. The new simmondsin derivative was isolated from jojoba meal by a combination of column chromatography and preparative HPLC and identified by 2D-NMR and L-SIMS as 2-(cyanomethylene)-3,4-dihydroxy-5-methoxycyclohexyl b-D-glucoside or 4-demethyl simmmondsin.

Evidences for a satiating effect of defatted jojoba meal

Abstract Supplementation of food with increasing doses (3, 5, and 10%) of defatted jojoba meal induced a pronounced dose-dependent food intake reduction in fasted and non-fasted rats. This effect was more pronounced in non-fasted than in fasted rats, which is typical for satiety agents. Water intake was reduced to the pair-fed level in non-fasted rats with free access to water and receiving food supplemented with 10% defatted jojoba meal. This was also observed in fasted rats deprived of water during the fasting period and receiving food supplemented with 10% defatted jojoba meal. The reduced water intake in defatted jojoba meal treated rats was entirely due to the food intake reduction. These observations are in favour of the hypothesis that defatted jojoba meal induces its food intake reduction by stimulating satiety. Possible mechanisms are discussed.

Simmondsin: effects on meal patterns and choice behavior in rats.

Simmondsin, a glycoside from jojoba meal, decreases food intake after oral administration. The present experiments are designed to clarify the mechanism of simmondsins anorectic activity. The meal pattern analysis shows that simmondsin supplementation at different doses results in a dose-dependent food intake reduction, which is more pronounced after prior simmondsin experience. The effect of simmondsin on meal patterns (decreased meal size, meal duration and eating rate, increased latency to eat) is most severe at the highest concentration. Rats familiar with simmondsin more seriously postpone their first meal than with first contact, resulting in a decrease of the meal frequency and the day/night feeding ratio. Rats given the choice between a control diet and a simmondsin-supplemented (0.5%) diet, after half an hour, have a significant preference for the control diet. Simmondsin seems to have a specific flavor when mixed in the food since rats recognise the feeder containing simmondsin. The ability of simmondsin to induce conditioned taste aversion (CTA) was also investigated. Rats receiving simmondsin at concentrations of 0.15%, 0.25% or 0.5% during their conditioning develop significant taste aversions to the saccharin solutions. The performed experiments indicate that the simmondsin activity shows some analogy with the satiating molecule cholecystokinin (CCK) at first contact, but shows more analogy with the illness-inducing agent lithium chloride (LiCl) after prior experience with simmondsin. Rats familiar with simmondsin avoid simmondsin-supplemented food by directly monitoring its presence, and by learning to relate it to the postingestive consequences of consumption.

Simultaneous determination of carbohydrates and simmondsins in jojoba seed meal (Simmondsia chinensis) by gas chromatography.

Separate methods for the analyses of soluble carbohydrates in different plants and simmondsins in jojoba seed meal are described. A reliable gas chromatographic procedure for the simultaneous quantification of D-pinitol, myo-inositoL sucrose, 5-alpha-D-galactopyranosyl-D-pinitol. 2-alpha-D-galactopyranosyl-D-pinitol, simmondsin, 4-demethylsimmondsin, 5-demethylsimmondsin and 4,5-didemethylsimmondsin as trimethylsilyl derivatives in jojoba seed meal has been developed. The study of different extraction mixtures allowed for the quantitative recovery of the 9 analytes by a mixture of methanol-water (80:20, v/v) in the concentration range between 0.1 and 4%. Comparison of the separation parameters on three different capillary stationary phases with MS detection allowed for the choice of the optimal gas chromatographic conditions for baseline separation of the analytes.

The vagus nerve is involved in the anorexigenic effect of simmondsin in the rat

Simmondsin, 2-(cyanomethylene)-3 hydroxy 4,5 dimethoxy cyclohexyl beta-D-glucoside, from jojoba meal reduces food intake in rats. We investigated the mechanism of action simmondsin, by studying the effects of fasting or of vagotomy on the food intake reduction. The food intake reduction was significantly less in fasted rats than in non-fasted rats. The reduction of food intake was also significantly diminished after vagotomy. The results of the present experiments suggest that simmondsin reduces intake of food in rats through the augmentation of satiety, in part vagally mediated.

Reproductive performance of rats treated with defatted jojoba meal or simmondsin before or during gestation

The effects on food intake, growth and reproductive performance parameters of defatted jojoba meal and pure simmondsin, an extract from jojoba meal, were compared in female Wistar rats. Rats fed 0.15% simmondsin or 3% defatted jojoba meal (equivalent to 0.15% simmondsin) for 8 weeks before conception showed a similar reduction in food intake (about 20%) and a similar growth retardation compared with controls. Both treatments induced a reduction in the number of corpora lutea on gestation day 16: this effect could be ascribed to the lower food intake before conception because it was also observed in rats pair-fed to the treated ones. Rats given feed containing 0.15% simmondsin or 3% defatted jojoba meal during days 1-16 of gestation showed a similar reduction in food intake relative to controls. Foetal and placental weights were reduced, relative to controls, to a similar extent in both groups, and the reductions were slightly greater than in the corresponding pair-fed groups. We conclude that the effects on food intake, growth and reproductive performance that were seen after feeding rats defatted jojoba meal were due to the simmondsin content of the meal. The simmondsin induced reduction in food intake and probably also a relative protein shortage.

Effects of simmondsin on food intake, growth, and metabolic variables in lean (+/?) and obese (fa/fa) Zucker rats

Incorporation of 2.5 g/kg of the anorexigen, simmondsin, in the diet resulted in food intake reduction in both lean and obese Zucker rats; however, the obese rats were much more sensitive to the food intake-reducing activity of simmondsin. In both obese and lean simmondsin-treated Zucker rats, growth was slower than in control rats, but was the same as that in pair-fed animals. The 24 h heat production pattern showed a smaller diurnal variation and a lower mean in obese rats than in lean rats. Food intake reduction, as a result of either simmondsin treatment or pair feeding, caused a decrease in mean heat production. Simmondsin treatment, but not pair feeding, caused a decrease in the diurnal variation of heat production. Plasma total cholesterol levels were increased in both simmondsin-treated and pair-fed obese and lean Zucker rats compared with control animals; this increase was mainly due to an increase in HDL-cholesterol levels. Blood leptin levels in both obese and lean rats decreased with decreased food intake and decreased fat deposition, but in obese rats, simmondsin treatment resulted in an additional decrease in leptin levels. It is concluded that the food intake-reducing effect of simmondsin is more pronounced in obese Zucker rats than in their lean littermates, and except for the simmondsin-specific effects on leptin and total cholesterol values in obese littermates, the effects of simmondsin are related to food intake restriction in obese and lean Zucker rats.

Hematological and pathological effects of 0.25% purified simmondsin in growing rats

Simmondsin, a glycoside extracted from jojoba meal (Simmondsia chinensis), causes a reduction in food intake after oral administration. To investigate whether a moderate dose of simmondsin, inducing a food intake reduction of about 25%, has transient or permanent detrimental effects on hematological and pathological parameters in rats, the following study was conducted. Rats treated with simmondsin (0.25% mixed in the food) were compared to the appropriate control- and pair-fed rats. After 10 weeks, 50% of the rats receiving simmondsin or pair-fed to simmondsin treated rats were changed to a control diet ad libitum, the other 50% remained on the simmondsin or pair-fed treatment until week 20. Growth, food intake, hematological and some pathological parameters were determined. From this study it could be concluded that simmondsin treatment induced a transient increase in organ weights compared to pair-fed rats, and a slight macrocytic, normochromic anemia, that also recovered completely after withdrawal of simmondsin. However, the conducted study did not reveal any microscopic or biochemical sign of toxicity.

Disruption of the behavioral satiety sequence by simmondsin.

Simmondsin, a cyanoglycoside from jojoba meal, reduces food intake after oral administration. To diagnose if it acts by inducing satiation or by creating abnormal physiological effects, an observational study was undertaken to investigate the effects of simmondsin on feeding and other behaviors. Particular attention was paid to the behavioral sequence associated with satiety (BSS). At first contact, simmondsin non-significantly reduced food intake by 17% and had little effect on feeding and associated behaviors. The behavioral structure was preserved and a small shift of the onset of resting to the left was observed, suggesting a small satiative action of simmondsin at first contact. Simmondsin given for the second time caused a more pronounced food intake reduction of 52% due to a reduction in eating duration, mean bout intake and mean bout length, and to an increase in latency to eat. At second contact, simmondsin caused a strong switching in active behaviors, disrupting the BSS. The simmondsin-induced hyperactivity suggests that simmondsin produces aversiveness with second contact. Our results indicate that simmondsin exerts multiple effects. It probably facilitates a small natural process of satiation/satiety at first contact, but creates abnormal physiological effects resulting in aversive reactions from second contact on.

Interlaboratory comparison of simmondsin analysis

Abstract Eleven samples containing various amounts of simmondsin (S), simmondsin ferulate (SF), demethyl simmondsins (DMS) and didemethyl simmondsins (DDMS) were analyzed by five different laboratories. The samples were made from chromatographically pure simmondsin, animal feed formulations containing jojoba meal, defatted jojoba meal, water extracts of jojoba meal and combinations of these ingredients. Where mixes were made, all materials were ground together in a coffee mill and sieved. Four laboratories analyzed for simmondsin and related components and one laboratory analyzed for only S. The means of the S, SF, DMS and DDMS percentages in the samples were determined to be: high performance liquid chromatography (HPLC) purified simmondsin, 94.1% S, 0 SF, 6.30% DMS, 0.52% DDMS; recrystallized simmondsin, 99.6% S, 0 SF, 1.01% DMS, 0 DDMS; water extract of jojoba meal 1, 29.2% S, 2.62% SF, 3.45% DMS, 9.47% DDMS; water extract of jojoba meal 2, 20.6% S, 2.00% SF, 2.81% DMS, 8.66% DDMS; formulated pet food with simmondsin, 0.59% S, 0 SF, 0 DMS, 0.01% DDMS; defatted jojoba presscake 7.05% S, 1.55% SF, 1.34% DMS, 3.48% DDMS. Using a Rank-Sum test, no laboratory demonstrated a consistently higher or lower bias compared to other laboratories for simmondsin analysis. Simmondsin analysis had less variability (C.V.=44) than other component analyses. Reproducibility for a blind duplicate sample of defatted jojoba presscake demonstrated that four of the five laboratories were consistent in simmondsin analysis. Water extracts of jojoba meal were shown to be highly variable in simmondsin content.