Article

Antidiabetic effect of d-limonene, a monoterpene in streptozotocin-induced diabetic rats

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Abstract

d-limonene (p-Menthal-1, 8-diene) is a monocyclic monoterpene obtained from orange, grape fruit and lemon. It exhibits a wide variety of pharmacological properties, including antioxidant, anti-inflammatory and anticarcinogenic activities. The present study evaluates the antidiabetic effect of d-limonene in streptozotocin-induced diabetic rats. Diabetes was induced in male albino rats of Wistar strain (180–200 g) by a single intraperitoneal injection of streptozotocin at a dose of 40 mg/kg body weight. d-limonene was administered orally at doses of 50, 100 and 200 mg/kg body weight and glibenclamide at a dose of 600 μg/kg body weight daily for 45 days. Plasma glucose and glycosylated hemoglobin levels were increased, the activities of gluconeogenic enzymes such as, glucose 6-phosphatase and fructose 1, 6-bisphosphatase were increased and the glycolytic enzyme, glucokinase activity was decreased along with liver glycogen in the diabetic rats. Graded doses of d-limonene reverse all the above changes towards normal level. The effect of d-limonene was more pronounced in 100 mg/kg body weight than the other two doses. The antidiabetic effect of d-limonene was comparable with glibenclamide. These findings suggest that d-limonene has potential antihyperglycemic activity in streptozotocin-induced diabetic rats.

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... D-lim group: D-lim (100 mg/kg) [32] was given orally, and saline (0.5 ml/day) was administrated intraperitoneally for 12 consecutive days. ...
... D-lim was administrated to animals 1 hour after intraperitoneal GM injection [35]. The dose (100 mg/kg) was selected according to a previous study representing the therapeutic effects of D-lim on streptozotocin-induced diabetes mellitus in rats [32]. Oral administrations were performed using gavage. ...
... Chemical structure of D-limonene (D-lim)[32]. ...
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Clinical application of gentamicin (GM) is well known to be associated with the development of acute kidney injury (AKI). This study was the first to investigate the possible protective effects of D-limonene (D-lim) on AKI following GM administration in rats. 32 rats arranged in four groups (n=8): (1) the control group received saline intraperitoneally (0.5 ml/day) and orally (0.5 ml/day), (2) the D-lim group received D-lim (100 mg/kg) orally and saline (0.5 ml/day) intraperitoneally, (3) the GM group received GM (100 mg/kg/day) intraperitoneally and saline (0.5 ml/day) orally, and (4) the treated group received intraperitoneal GM (100 mg/kg) and oral D-lim (100 mg/kg). All treatments were performed daily for 12 consecutive days. Results revealed that D-lim ameliorated GM-induced AKI, oxidative stress, mitochondrial apoptosis, and inflammation. D-lim showed nephroprotective effects as reflected by the decrease in serum urea and creatinine and improvement of renal histopathological changes. D-lim alleviated GM-induced oxidative stress by increasing the activities of renal catalase, serum and renal glutathione peroxidase, and renal superoxide dismutase and decreasing renal malondialdehyde and serum nitric oxide levels. Intriguingly, D-lim suppressed mitochondrial apoptosis by considerably downregulating Bax and caspase-3 (Casp-3) mRNA and protein expressions and markedly enhancing Bcl2 mRNA and protein expressions. Furthermore, D-lim significantly decreases GM-induced inflammatory response through downregulation of NF-κB, IL-6, and TNF-α mRNA and/or protein expressions and decrease in renal myeloperoxidase activity. Finally, D-lim remarkably downregulated PCNA protein expression in the treated group compared with the GM group. In brief, this study showed that D-lim alleviated AKI following GM administration in rats, partially through its antioxidant, anti-inflammatory, and antiapoptotic activities as well as downregulation of PCNA expression.
... In our previous study, we showed that D-limonene could ameliorate acute kidney injury following gentamicin administration (22). Additionally, it has been demonstrated that D-limonene alleviated gallstone-and doxorubicin-induced renal damages (23). To the best of our knowledge, there are no studies on the effects of D-limonene pretreatment on RIR in rats. ...
... Design of the experiment: The rats were randomly divided into 3 equal groups (n=8): group 1 (healthy control); group 2 (RIR): these animals underwent RIR and received normal saline (1 mL/kg) every day by oral gavage. Group 3 underwent RIR and received D-limonene (100 mg/kg) every day by oral gavage (23). Pretreatment began 12 days before RIR induction on a daily basis. ...
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Background and Objective: Reactive oxygen species are the main factors involved in kidney damage during renal ischemia-reperfusion (RIR). Since D-limonene has antioxidant, anti-diabetic, anti-apoptotic, and lipid peroxidation effects, it prevents mitochondrial dysfunction and inhibits ROS, this study was conducted to evaluate the effects of pretreatment with D-limonene on oxidative stress and antioxidant activity in RIR injury. Methods: In this experimental study, 24 male Wistar rats were randomly divided into 3 groups: control, RIR (ischemia was induced by clamping of renal pedicles for 45 minutes and reperfusion was considered 24 hours after ischemia), and RIR+D-limonene (100 mg/kg by oral gavage for 12 days). Serum and kidney were used to evaluate malondialdehyde (MDA), myeloperoxidase (MPO), paraoxonase1 (PON1), glutathione (GSH), catalase (CAT), glutathione peroxidase (GPX), and nitric oxide (NO). Findings: Serum and renal levels of MDA ([18.2±98.77 vs. 9.21±1.77] and [19.85±3.39 vs. 9.84±1.65]) and MPO ([67.25±32.67 vs. 40.21±6.1] and [18.44±2.86 vs. 10.42±1.68]) and serum level of NO (31.3±36.1 vs. 27.88±2.6) significantly increased in the RIR group compared with the control group (p<0.05). Serum and kidney levels of GSH, activities of CAT and GPX in serum and kidney, and serum activity of PON1 significantly decreased in the RIR group compared with the control group (p<0.05). Pretreatment with D-limonene could significantly ameliorate serum and renal levels of MDA, serum levels of GSH and NO, and serum activity of CAT in rats pretreated with D-limonene in comparison with RIR rats (p<0.05). Conclusion: This study indicated that pretreatment with D-limonene could ameliorate RIR injuries in rats through its antioxidant activities.
... But these have been revealed to have detrimental side-effects such as weigh gain and severe hypoglycemia (More et al., 2014). Studies have shown anti-diabetic effect of d-limonene in streptozotocin induced diabetes in murine models (Bacanlı et al., 2017;Murali & Saravanan, 2012). Murali et al demonstrated that the administration of d-limonene in streptozotocin induced diabetic rats reduced blood glucose level, glycosylated hemoglobin (indicator of diabetes) and increased plasma insulin and carbohydrate metabolizing enzymes. ...
... Murali et al demonstrated that the administration of d-limonene in streptozotocin induced diabetic rats reduced blood glucose level, glycosylated hemoglobin (indicator of diabetes) and increased plasma insulin and carbohydrate metabolizing enzymes. The D-limonene administration to diabetic rats also reduced the activity of enzymes involved in gluconeogenesis (Murali & Saravanan, 2012). In another study, also Dlimonene reduced the blood glucose level and increased the plasma insulin levels in streptozotocin induced diabetic rats (Bacanlı et al., 2017). ...
Article
Citrus rinds contain a tremendous amount of essential oils. The peels contain majority of the essential oils that are continuously wasted. One of the major constituents of the essential oils in the zest of different citrus fruits like orange, tangerine, lemon and grapefruit is limonene. The review aims at discussing various conventional and novel extraction methods of limonene from citrus fruits. The review also discusses various therapeutic properties of limonene and the mechanism behind these properties. Limitations in the use of limonene such as toxicity and side-effects will be delineated. Limonene is present in the range of 26.9-97.83% in the citrus essential oils. The percentage of limonene in the essential oil depends on the Citrus species and extraction methodology. There are different extraction methods such as hydrodistillation, steam distillation, cold pressing, microwave-assisted extraction, ultrasound sound assisted extraction and supercritical fluid extraction. Various therapeutic potential of limonene has been reported. Limonene is usually non-toxic but its epoxides can be toxic at the very high dose. This up to date and comprehensive review aims to provide a valuable overview of limonene and its therapeutic potential.
... Anti-inflammatory [15], antidiabetic effects [16], immunomodulatory activity [17], analgesic [18], hypolipidemic and antioxidant activities [19], antimicrobial activity [20], anticancer activity [20], insecticidal activity [20] β-Phellandrene c C 10 Anti-inflammatory and analgesic [23], anticonvulsant [24], gastric protection effects [25] Anti-inflammatory [29], antibacterial [30], antischistosomiasis [31] Note: VIP > 1.5 and p < 0.01. e symbol "-" stands for none. ...
... Given that the EO of HC exerts various pharmacological activities [2,3], we explored whether the above chemical markers possess these activities. As present in Table 2, five chemical markers (α-pinene, limonene, β-phellandrene,α-terpineol, and n-hexadecanoic acid) between DHC and FHC and three chemical markers (β-myrcene, β-phellandrene, and phytol) in FHC at two harvest seasons exhibit a wide range of pharmacological activities including anti-inflammatory, ant-oxidant, antiallergy, antibacterial, antiviral, immunologic, anticancer, antianxiety, analgesic, and antidiabetic effects [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. erefore, the different contents of these chemical markers in DHC and FHC and the two harvest seasons of FHC might influence the quality and efficacy. ...
Article
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Houttuyniae Herba (HH) refers to the dried aerial part of Houttuynia cordata Thunb. (DHC) or the fresh whole grass of Houttuynia cordata Thunb. (FHC), where DHC are harvested in summer and FHC around the year. However, harvest seasons and processing methods (i.e., medicinal parts and drying process) might affect the quality of HH. To compare the essential oils (EOs) of DHC and FHC and their two harvest seasons, GC-MS analysis combined with chemometric analysis was applied. The results showed that the oil yield of FHC (0.076 ± 0.030%) was higher than that of DHC (0.038 ± 0.029%), and oil yield was higher in summer than in autumn (0.044 ± 0.029% for DHC1, 0.036 ± 0.028% for DHC2, 0.084 ± 0.026% for FHC1, and 0.067 ± 0.033% for FHC2, respectively). Moreover, hierarchical cluster analysis (HCA) and principal component analysis (PCA) successfully distinguished the chemical constituents of DHC and FHC oils. Additionally, according to orthogonal partial least squares discriminant analysis (OPLS-DA), eleven components were selected as chemical markers for discriminating DHC and FHC, and two and four chemical markers for discriminating two harvest seasons of DHC and FHC, respectively. Among these markers, the average contents of α-pinene, limonene, β-phellandrene, α-terpineol, 4-tridecanone, and ethyl decanoate were higher in FHC oils. In contrast, the average contents of nonanal, 1-nonanol, β-cyclocitral, n-hexadecanoic acid, and octadecanol were higher in DHC oils. Additionally, the contents of 4-tridecanone and ethyl decanoate were both higher in DHC1 oils than in DHC2 oils. Moreover, the contents of β-myrcene and β-phellandrene were higher in FHC1 oils, while the contents of 2,6-octadien-1-ol, 3,7-dimethyl-, acetate, and (z)-phytol were higher in FHC2 oils. For these reasons, this study provides a scientific basis for quality control and clinical medication.
... But these have been revealed to have detrimental side-effects such as weigh gain and severe hypoglycemia (More et al., 2014). Studies have shown anti-diabetic effect of d-limonene in streptozotocin induced diabetes in murine models (Bacanlı et al., 2017;Murali & Saravanan, 2012). Murali et al demonstrated that the administration of d-limonene in streptozotocin induced diabetic rats reduced blood glucose level, glycosylated hemoglobin (indicator of diabetes) and increased plasma insulin and carbohydrate metabolizing enzymes. ...
... Murali et al demonstrated that the administration of d-limonene in streptozotocin induced diabetic rats reduced blood glucose level, glycosylated hemoglobin (indicator of diabetes) and increased plasma insulin and carbohydrate metabolizing enzymes. The D-limonene administration to diabetic rats also reduced the activity of enzymes involved in gluconeogenesis (Murali & Saravanan, 2012). In another study, also Dlimonene reduced the blood glucose level and increased the plasma insulin levels in streptozotocin induced diabetic rats (Bacanlı et al., 2017). ...
Article
Full-text available
Citrus rinds contain a tremendous amount of essential oils. The peels contain majority of the essential oils that are continuously wasted. One of the major constituents of the essential oils in the zest of different citrus fruits like orange, tangerine, lemon and grapefruit is limonene. The review aims at discussing various conventional and novel extraction methods of limonene from citrus fruits. The review also discusses various therapeutic properties of limonene and the mechanism behind these properties. Limitations in the use of limonene such as toxicity and side-effects will be delineated. Limonene is present in the range of 26.9-97.83% in the citrus essential oils. The percentage of limonene in the essential oil depends on the Citrus species and extraction methodology. There are different extraction methods such as hydrodistillation, steam distillation, cold pressing, microwave-assisted extraction, ultrasound sound assisted extraction and supercritical fluid extraction. Various therapeutic potential of limonene has been reported. Limonene is usually non-toxic but its epoxides can be toxic at the very high dose. This up to date and comprehensive review aims to provide a valuable overview of limonene and its therapeutic potential
... In another study, the oral administration of Dlimonene decreased plasma glucose, glycosylated hemoglobin levels, activities of gluconeogenic enzymes such as glucose 6phosphatase and fructose 1, 6 bisphosphatase with the increased activity of the glycolytic enzyme, glucokinase, and liver glycogen in the diabetic rats. The pronounced effect of Dlimonene was observed at a dose of 100 mg/kg body weight and comparable with glibenclamide (Murali and Saravanan 2012). Total triterpene acid (TTA) fractions from the leaves of Eriobotrya japonica have shown the hypoglycemic and hypolipidemic effect in both alloxan and STZ induced diabetic mice. ...
Article
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Type II diabetes is a metabolic disorder characterized by hyperglycemia arising from defective insulin signaling. Several synthetic drugs are being used for diabetes treatment, but they have adverse effects. So as an alternative approach, compounds from plants with lesser/no side effects and comparatively cheaper are gaining momentum. Terpenes comprise a class of diversified phytochemicals, which have beneficial effects and important functions in plants. They have shown a series of biological properties that health­promoting conduct in humans. Besides, a lot of terpenes have also been reported to be much less toxic as compared to synthetic compounds. Diabetic people could be benefited from terpenes obtained either from the diet or from plant-derived herbal medicines. Due to the natural origin of terpenes, they are supposed to be a safe and promising agent in eliminating the causes and effects of diabetes. This paper reviews the research reports of terpenes as their antidiabetic potential, mechanistic action, preclinical profile, shortcomings, and prospect in the effective management of diabetes.
... [34 -38] The cyclic monoterpene, Limonene, detected in substantial amount (7.1 %) in the tested EO, is commonly found in citrus fruits and reputed for several biological attributes including antioxidant, anti-inflammatory, antidiabetic, and antitumor. [39,40] The chemical composition of the EO in this study is very different from specimen of T. asiatica that has been previously reported. For instance, the most abundant compounds in EO extracted from T. asiatica grown in India, where the most abundant was β-Phellandrene (21.4 %), cisocimene (12.9 %), α-phellandrene (9.01 %), viridiflorol (6.74 %), β-bisabolol (5.24 %) and α-pinene (4.49 ...
Article
Toddalia asiatica (L.) Lam. is extensively used in traditional medicinal systems by various cultures. Despite its frequent use in traditional medicine, there is still a paucity of scientific information on T. asiatica growing on the tropical island of Mauritius. Therefore, the present study was designed to appraise the pharmacological and phytochemical profile of extracts (methanol, ethyl acetate and water) and essential oil obtained from aerial parts of T. asiatica. Biological investigation involved the evaluation of in vitro antioxidant and enzyme inhibitory potentials. The chemical profile of the EO was determined using gas chromatography coupled to mass spectrometry (GC/MS) analysis, while for the extracts, the total phenolic (TPC) and flavonoid content were quantified as well as their individual phenolic compounds by LC/MS/MS. Quinic acid, fumaric acid, chlorogenic acid, quercitrin and isoquercitrin were the main compounds in the extracts. Highest total phenolic (82.5±0.94 mg gallic acid equivalent (GAE/g)) and flavonoid (43.8±0.31 mg rutin equivalent (RE/g)) content were observed for the methanol extract. The GC/MS analysis has shown the presence of 26 compounds with linalool (30.9 %), linalyl acetate (20.9 %) and β‐phellandrene (7.9 %) being most abundant components in the EO. The extracts and EO showed notable antioxidant properties, with the methanol extract proved to be superior source of antioxidant compounds. Noteworthy anti‐acetylcholinesterase (AChE) and anti‐butyrylcholinesterase (BChE) effects were recorded for the tested samples, while only the methanol and ethyl acetate extracts were active against tyrosinase. With respect to antidiabetic effects, the extracts and EO were potent inhibitors of α‐glucosidase, while modest activity was recorded against α‐amylase. Docking results showed that linalyl acetate has the highest affinity to interact with the active site of BChE with docking score of −6.25 kcal/mol. The findings amassed herein act as a stimulus for further investigations of this plant as a potential source of bioactive compounds which can be exploited as phyto‐therapeutics.
... Dang [46] did not obtain a-glucosidase-inhibitory activity for pomelo EO from Vietnam. According to Dang et al. [46], D-limonene was the main abundant compound in pomelo oils; although this is presented in the literature as an antidiabetic phytochemical, it is not responsible of the carbohydrate-hydrolysing enzyme-inhibitory activity [47,48]. On the contrary, α-pinene, β-pinene 1,8-cineole, 4-terpineol, and α-terpineol resulted in being able to inhibit α-amylase [49], and the activity of the EO is often the result of an antagonistic or additive effect between the constituents of the oil. ...
Article
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The aim of the present study is to investigate the chemical profile, antioxidant activity, carbohydrate-hydrolysing enzyme inhibition, and hypolipidemic effect of essential oils (EOs) extracted from Sicilian Citrus maxima (pomelo) flavedo. Using gas-chromatography-mass spectrometry analysis (GC-MS) we analysed the Eos of five cultivars of C. maxima, namely, ‘Chadock’, ‘Maxima’, ‘Pyriformis’, ‘Terracciani’, and ‘Todarii’, and their blends. The antioxidant activity was performed by using a multi-target approach using 2,2′-Azino-Bis-3-Ethylbenzothiazoline-6-Sulfonic acid (ABTS), 2,2-Diphenyl-1-picrylhydrazyl (DPPH), ferric reducing ability power (FRAP), and β-carotene bleaching tests. The α-amylase, α-glucosidase, and lipase-inhibitory activities were also assessed. GC-MS analyses revealed D-limonene as the main monoterpene hydrocarbon in all cultivars, albeit with different percentages in the range of 21.72–71.13%. A good content of oxygenated monoterpenes was detected for all cultivars, especially for ‘Todarii’. The analysis of the principal components (PCA), and related clusters (HCA), was performed to find chemo-diversity among the analysed samples. EOs from ‘Chadock’ and ‘Maxima’ were statistically similar to each other, and they differed from P3 in the smaller amount of sesquiterpene hydrocarbons, while the oils from ‘Terracciani’ and ‘Todarii’ were found to be chemically and statistically different. ‘Chadock’ EO was the most active to scavenge radicals (IC50 values of 22.24 and 27.23 µg/mL in ABTS and DPPH tests, respectively). ‘Terracciani’ EO was the most active against both lipase and α-amylase, whereas the blends obtained by the combination (1:1 v/v) of C. maxima ‘Maxima’ + ‘Todarii’ were the most active against α-glucosidase. Generally, the blends did not exert a unique behaviour in potentiating or reducing the bioactivity of the pomelo EOs.
... Moreover, the emerging evidence about the healing properties of limonene, such as antinflammatory, chemopreventive and antiproliferative ones, stimulated the scientific interest for its medicinal and dietary applications [17,[30][31][32][33][34]. For instance, limonene it has been used clinically to relieve gastric acid-induced heartburn [35]; other studies suggest that D-limonene may have beneficial effects in diabetes mellitus [36]. ...
Article
The interaction of limonene, terpineol, and 1,8 cineol with a model of biological membrane and the absorption of the three compounds by the same model of biological membrane were studied. In addition, the possibility to use a lipophilic carrier for the transport and delivery of the compounds to the biomembrane was investigated. Differential scanning calorimetry technique was used. The obtained results reveal that all the compounds interact and are absorbed by the model of biomembrane with different extent depending on their characteristics. Moreover, the lipophilic carrier could be used as a suitable system for the transport and delivery of such compounds to biomembranes.
... It has been categorized as a green biodegradable and non-toxic solvent instead of hazardous petroleum based-solvents, because it can effectively be used for lipid extraction from microalgae or plant matrices [20], [21]. Moreover, D-Limonene has the antioxidant potential, anti-diabetic effect and other clinical applications, so that it is recommended to be used for nhexane substitute [22]- [25]. ...
Article
Full-text available
Palm oil is one of the main agricultural commodities in Indonesia. Beside CPO and PKO as the main downstream product, the palm oil industry also produces solid wastes such as shells, fibers, and palm oil empty fruit bunches (EFB). Palm oil EFBs are often dumped nearby the palm oil plantations and being left to be decomposed, but several literature studies indicated that palm oil EFB still contained oil residue rich in β - carotene as well as other lipids components dissolved on it. β - carotene is among the major products of the food industry which have been widely employed as nutrients, food colorants, and additives. It serves as antioxidants and so-called pro-vitamin A. The previous research used n-Hexane as a solvent in β - carotene extraction from fungal - fermented palm oil EFB, whereas n-Hexane has a moderate toxicity level and low solubility of β - carotene which is only 600 ppm. Quality and food safety aspects of β - carotene extract haven’t been reviewed or analyzed yet. This paper will be focused on the food safety analysis and improvement concept that can be applied in the extraction method and appropriate solvent selection to obtain high-quality extracts of food-grade β - carotene from fungal - fermented palm oil EFB. Toxicity level and the Hansen Solubility Parameter (HSP) simulation results are the main criteria for solvent selection, while thermal stability, operational cost, and practical aspects are being considered to choose a better extraction method. Based on the HSP simulation results and all criteria mentioned before, n-Hexane can be substituted with 3 recommended solvents; D-Limonene, Tetrahydrofuran (THF), or Tetrahydrofurfuryl Alcohol. According to the economic analysis, the maceration method using THF at room temperature is being preferred to the soxhletation method. Moreover, food safety analysis is being reviewed based on HACCP principles.
... As a result, they have been accepted as flavoring agents in food products including alcoholic and nonalcoholic beverages, jellies, marmalades, candies, dairy products, and cakes (Karoui et al., 2010). Furthermore, they are plant secondary metabolites with a wide variety of pharmacological and biological potentials, such as anti-inflammatory, antioxidant and antimicrobial activities (Calo et al., 2015;Murali and Saravanan, 2012). ...
Article
In this research, hydrodistillation ultrasonic‐assisted green technique was applied to extract the essential oils from bitter orange peel. The effects of independent factors (volume/mass ratio (X1), ultrasonic time (X2) and hydrodistillation extraction time (X3)) on the quantitative, phenolic and antioxidant properties of essential oils were investigated. Linear and quadratic polynomial models with suitable ANOVA results (model p‐values <0.0003, R2 values of 0.84‐0.95, adjusted R2 values of 0.82‐0.90, predicted R2 values of 0.71‐0.75, and lack of fit p‐values >0.5) were used for fitting the responses. Two optimal extraction conditions for bitter orange peel essential oils were determined as follows: optimum responses (OR) with maximum essential oil volume (0.99 ml), maximum TPC (108.33 mg GAE/100 ml) and minimum IC50 (251.56 µl) could be achieved at X1: 6.00 ml/g, X2: 39.10 min and X3: 4.72 h, and optimum phenolic compounds (OP) with maximum TPC of 190.75 mg GAE/100 ml could be obtained at X1: 13.89 ml/gr, X2: 3.75 min and X3: 4.92 h. The most predicted values for optimum conditions were in good agreement with experimental data. The disk diffusion experiments showed high antimicrobial activities of the optimum essential oils against E. coli. The GC‐MS results proved limonene was the main compound in both optimum essential oils. These bitter orange peel essential oils with suitable antioxidant and antimicrobial activities, and healthy compositions, could be considered as dietary and pharmaceutical supplements.
... 19 Limonene (triterpenoid) causes the stimulation of insulin secretion due to the regenerated cell, lower the blood glucose, and modulate the critical enzymes of carbohydrate metabolism (increased glycolysis and decreased gluconeogenesis). 20 Tannic acid causes a lowering of blood glucose levels. It enhances the glucose utilization by inducing glucose transporters and through activation of insulin-mediated signaling pathways. ...
Article
Diabetes is a chronic metabolic disorder characterized by a high blood glucose concentration, i.e., hyperglycemia or caused by insulin deficiency, often combined with insulin resistance. In the Present study, the antidiabetic and antioxidant activity of the methanolic extract of Tagetes patula flower heads was screened out in rodent models. The pharmacological evaluation was carried out using 200 and 400 mg/kg, b.w. The in-vivo antidiabetic activity was performed in streptozotocin, dexamethasone-induced diabetic models and oral glucose tolerance test. Metformin hydrochloride was used as a standard. The parameters like blood glucose levels, insulin levels, homeostasis assessment of insulin resistance, insulin sensitivity, and fasting glucose-insulin ratio were estimated in these models. The in-vitro antioxidant activity of methanolic extract of Tagetes patula was performed by using hydroxyl radical scavenging assay and Ascorbic acid was used as a standard. The preliminary phytochemical screening of Tagetes patula revealed the presence of phytoconstituents like alkaloids, flavonoids, saponins, steroids, phenols, carbohydrates, triterpenoids, and tannins. The extract showed a significant decrease in the elevated blood glucose levels in streptozotocin, dexamethasone-induced diabetic models, and also in the oral glucose tolerance test. The extract prevented insulin resistance and significantly increased insulin sensitivity in the dexamethasone-induced model. The various phytochemical constituents like alkaloids, flavonoids, saponins, steroids, and phenols might be responsible for lowering the blood glucose levels in the animal models mentioned above. The extract showed significant scavenging activity against hydroxyl free radicals. From the above outcomes, it is flawless that the methanolic extract of Tagetes patula has antidiabetic and antioxidant activities.
... Curcume and Zingeberene, along with Alpha-curcumen performs as an antioxidant and antibacterial [17,21,22], further Zingeberene inhibits cancer cells growth [28]. D-limonene has biological activities widely, involving anti-diabetic [29], anti-carcinogenic, anti-oxidant, and anti-inflammatory effects [30]. Isopropylbenzene (cumene) is also identified in Cuminum cyminum, Cinnamomum verum, and Zingiber officinal [31]. ...
... Babukumar et al. studied that Geraniol (15), a natural monoterpene, having an insulinotropic potential, refurbished glucose homeostasis by altering the activities of GK and G6P (Babukumar et al. 2017). Similarly, D-limonene (11), a monoterpene present in citrus fruits, lowers BG level by modulating key carbohydrates metabolic enzymes present in the liver (Murali and Saravanan 2012). Asiatic acid (4) and Ursolic acid (25) are two main pentacyclic triterpenoids that maintain normal glucose homeostasis by amplifying the conversion of glucose into glycogen and impeding hepatic glucose production (Jang et al. 2010;Ramachandran and Saravanan 2013). ...
Article
Traditional medicinal plants have wide-reaching utilisation in the treatment of diabetes especially in developing countries where medical resources are meagre. Traditionally used anti-diabetic plants act by numerous mechanisms, however, only a few of them act through activation of the glucokinase enzyme. Glucokinase is a key regulatory enzyme in glucose metabolism thereby controls glucose homeostasis and insulin secretion. The present review significantly analyses the knowledge about various plant-based glucokinase activators including numerous phyto-chemicals which modulate the activity and gene expression of glucokinase and would provide data support and perspective regarding future research in the discovery and development of different plant-derived glucokinase activators. ARTICLE HISTORY
... The blood glucose levels, total cholesterol, and triglyceride levels in the limonene treated diabetic rats were lower than in the control group [35]. Limonene treatment also reversed the changes in plasma HbA1C levels, the activities of gluconeogenic enzymes such as glucose 6-phosphatase and fructose 1,6bisphosphatase, and the glucokinase activity [36]. ...
Article
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Insulin plays a significant role in carbohydrate homeostasis as the blood glucose lowering hormone. Glucose-induced insulin secretion (GSIS) is augmented by glucagon-like peptide (GLP-1), a gastrointestinal peptide released in response to ingesting nutriments. The secretion of insulin and GLP-1 is mediated by the binding of nutrients to G protein-coupled receptors (GPCRs) expressed by pancreatic β-cells and enteroendocrine cells, respectively. Therefore, insulin secretagogues and incretin mimetics currently serve as antidiabetic treatments. This study demonstrates the potency of synthetic isoprenoid derivatives of lysophosphatidylcholines (LPCs) to stimulate GSIS and GLP-1 release. Murine insulinoma cell line (MIN6) and enteroendocrinal L cells (GLUTag) were incubated with LPCs bearing geranic acid (1-GA-LPC), citronellic acid (1-CA-LPC), 3,7-dimethyl-3-vinyloct-6-enoic acid (GERA-LPC), and (E)-3,7,11-trimethyl- 3-vinyldodeca-6,10-dienoic acid (1-FARA-LPC). Respective free terpene acids were also tested for comparison. Besides their insulin- and GLP-1-secreting capabilities, we also investigated the cytotoxicity of tested compounds, the ability to intracellular calcium ion mobilization, and targeted GPCRs involved in maintaining lipid and carbohydrate homeostasis. We observed the high cytotoxicity of 1-GERA-LPC and 1-FARA-LPC in contrast 1-CA-LPC and 1-GA-LPC. Moreover, 1-CA-LPC and 1-GA-LPC demonstrated the stimulatory effect on GSIS and 1-CA-LPC augmented GLP-1 secretion. Insulin and GLP-1 release appeared to be GPR40-, GPR55-, GPR119- and GPR120-dependent.
... In one of these studies, El-Soude et al. evaluated the essential oil of seed of F. vulgare for its hypoglycaemic effect and found that the oil had good antidiabetic activity [64]. Also, previous studies have shown that limonene has antidiabetic activity [65]. Therefore, limonene and other compounds may be responsible for the activity of the essential oil obtained from DEO, which exhibits an important antidiabetic activity in our current study. ...
Article
The chemical composition of essential oils of aerial parts of Daucus carota (DEO) and Foeniculum vulgare (FEO) was specified by GC/MS. Antidiabetic, anti-inflammatory, antioxidant, and antibacterial activities of oils were tested by -glucosidase inhibitory, 5 lipoxygenase inhibitory, DPPH/ABTS radical scavenging, and broth microdilution methods, respectively. Thirty components were identified in DEO (87.7%). Carotol (27.7%), elemicin (18.1%), and limonene (16.0%) were determined as the main compounds in DEO. Seventeen constituents were identified in FEO (100.0%). Estragole (34.0%), limonene (27.1%), and -pinene (19.5%) were found as major components in FEO. Both oils displayed weak antibacterial activity against Gram-negative bacteria. However, the oils were not effective on Grampositive bacteria. DEO with IC50 values of 1359 and 1579 μg/mL and FEO with IC50 values of 3106 and 1654 μg/mL showed weak antioxidant activities against DPPH and ABTS radicals, respectively. DEO and FEO exhibited good antilipoxygenase activities with IC50 values of 87.24 and 58.35 μg/mL, respectively. DEO presented significantly -glucosidase inhibitory activity with an IC50 value of 44.78 µg/mL while FEO displayed poor activity with an IC50 value of 1967 µg/mL. This study is the first report on the 5-lipoxygenase and -glucosidase inhibitory activities of aerial parts of DEO as well as on the -glucosidase inhibitory activity of aerial parts of FEO. These results indicated that DEO, which has a good antidiabetic and anti-inflammatory activity, is rich in oxygenated sesquiterpene and monoterpene. Also, it showed that FEO, which has a significant anti-inflammatory activity, is rich in monoterpene and phenylpropanoid.
... It also promoted the activities of glucokinase and glucose-6-phosphate dehydrogenase in the liver and protected pancreatic islets [44]. is monoterpene inhibited the activity of α-amylase (IC 50 � 152.3 ± 1.21 μg mL −1 ), α-glucosidase (IC 50 � 94.02 ± 0.78 μg mL −1 ) [45], and β-galactosidase [46]. On the other hand, limonene ameliorates glucose homeostasis by increasing hepatic glycogen with a decrease in plasma glucose and HbA 1c levels and suppresses the activities of gluconeogenic enzymes (G6Pase and FBPase) [47]. Moreover, it ameliorates the reduction of FBG level and glucose tolerance along with the activation of PPARα signaling [48]. ...
Article
Full-text available
Origanum elongatum L. is an endemic aromatic and medicinal plant. This work reports previous studies on O. elongatum concerning its taxonomy, botanical description, geographical distribution, bioactive compounds, toxicology, and biological effects. Chemical analyses showed that O. elongatum contains different chemical compounds, in particular volatile compounds. Pharmacological investigations showed that volatile compounds and extracts from O. elongatum exhibit different pharmacological properties, such as antibacterial, antifungal, antiviral, antioxidant, vasodilator, corrosion inhibitor, and hepatoprotective effects. Moreover, toxicological reports revealed the safety of this species. The pharmacological effects of O. elongatum could be correlated with the main compounds, which exhibit different pharmacological properties with numerous mechanism insights.
... This can be found in the Rutaceae family. The monoterpene has various biological effects, including neuroprotective, anti-diabetic, anti-inflammatory, and antioxidant [136,137]. Its activity against neurodegeneration symptoms, namely memory impairment and hippocampal damage, was investigated by in vivo testing, i.e., the Morris water maze and elevated plus-maze tests. ...
Article
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Alzheimer’s disease (AD) is the leading cause of dementia and cognitive function impairment. The multi-faced character of AD requires new drug solutions based on substances that incorporate a wide range of activities. Antioxidants, AChE/BChE inhibitors, BACE1, or anti-amyloid platelet aggregation substances are most desirable because they improve cognition with minimal side effects. Plant secondary metabolites, used in traditional medicine and pharmacy, are promising. Among these are the monoterpenes—low-molecular compounds with anti-inflammatory, antioxidant, enzyme inhibitory, analgesic, sedative, as well as other biological properties. The presented review focuses on the pathophysiology of AD and a selected group of anti-neurodegenerative monoterpenes and monoterpenoids for which possible mechanisms of action have been explained. The main body of the article focuses on monoterpenes that have shown improved memory and learning, anxiolytic and sleep-regulating effects as determined by in vitro and in silico tests—followed by validation in in vivo models.
... Moreover garlic contain allicin , cysteine sulfoxide, and S-allyl cysteine sulfoxide and these compounds reduced the level of glucose by several mechanism that include, enhancing the secretion of insulin from beta cells, increasing the cell sensitivity to insulin and preventing the insulin activation caused by liver, the activity of allicin in reducing blood glucose in rats was similar to that investigated by insulin and glibenclamide. Garlic oil also was reported to decrease the serum alanine transferases ,amylase and aspartate in diabetic rats [22].The limonene effects include stimulation of insulin secretion ,regeneration of β-ells, amelioration of secondary complications of higher blood glucose such as hyperlipidaemia via inhibition of liver x receptors signaling pathway, modulation of transcription factors such as activation of peroxisome proliferator-activated receptors and modulation of rate limiting enzymes of carbohydrate metabolism [23,24] , garlic and citrus extract contain flavonoids which have anti-diabetic effect through their ability to modulate glucose metabolism or insulin sensitivity at different levels, increase glucose uptake and insulin secretion, and inhibit glucose production [25] Also this results could be attributed to the antioxidant vitamins present in garlic and citrus extract . The mechanism of action could be explained through the ability of the antioxidant vitamins to scavenge free radicals preventing alloxan-induced oxidative stress and protecting the β cells. ...
Article
Full-text available
The current study was designated to investigate the effect of Allium sativum and Citrus aurantifolium plants (C. aurantifolium) extract on blood glucose and lipid profile as well as body weight in diabetic rats, thirty adult rats were divided into five groups (6rat for each). G1 :served as healthy control given tap water G2 :diabetic without treatment , G3: diabetic treated with garlic extract 150 mg\kg body weight, G4:diabetic treated with C. aurantifolium and G5: group treated with150 mg\kg mix extracts (garlic and C. aurantifolium).All treated animals were given orally 1 ml of extracts every day. The effects of aqueous extract of garlic and C. aurantifolium on some parameters were investigated in normal and diabetic rats such as fasting blood sugar(FBS), fasting serum insulin(F.serum insulin) ,ketone body , lipid profile (Cholesterol , Triglyceride, High density lipoprotein(HDL),and Low density lipoprotein LDL) , the results investigated a significant decrease in glucose levels in group treated with mix plants(159.73±2.67) as compared with garlic (176.10±2.69) and C. aurantifolium (205.45±4.09) after twenty days of treatment, also the results display a significant improvement in insulin level in groups which treated with garlic , C. aurantifolium and mix plants (4.61±1.22 ,3.69±1.03 and 4.21±1.50 mg\dl respectively) compared with untreated diabetic group (1.88±0. 60), the value of ketone body was decreased in all treated groups with garlic, C. aurantifolium and mix plants(5.73±1.98, 6.94±2.86 and4.90±1.84) respectively, the results report a significant decline in cholesterol level in groups treated with garlic ,C. aurantifolium and mix extract (91±3.98, 95±4.35 and 87±2.45)mg\dl respectively compared with the untreated diabetic group (108±3.08 mg\d). the level of Triglyceride reported a significant p<0.05 decrease in all groups treated with garlic ,C. aurantifolium and mix extract (89±3.96, 90±3.78 and 85±3.73) mg/dl respectively compared with untreated diabetic group (102±4.43) mg\dl. HDL level revealed significant p<0.05 improvement in groups treated with garlic ,C. aurantifolium and mix extract(38±2.94, 32±2.09 and 42±3.02) mg\dl compared with control and untreated diabetic groups (30±2.12 and 24±3.53) mg\dl , reduced level of LDL were assessed in groups treated with garlic ,C. aurantifolium and mix extract(40±3.59, 43±4.50 and30±3.42) mg\dl. There was a significant p<0.05 improvement in body weight in the group treated with mix plants extract (184 ±4.30 g) after 30 days as compared with these groups at the beginning of experiment (178 ±2.93) g.
... Moreover garlic contain allicin , cysteine sulfoxide, and S-allyl cysteine sulfoxide and these compounds reduced the level of glucose by several mechanism that include, enhancing the secretion of insulin from beta cells, increasing the cell sensitivity to insulin and preventing the insulin activation caused by liver, the activity of allicin in reducing blood glucose in rats was similar to that investigated by insulin and glibenclamide. Garlic oil also was reported to decrease the serum alanine transferases ,amylase and aspartate in diabetic rats [22].The limonene effects include stimulation of insulin secretion ,regeneration of β-ells, amelioration of secondary complications of higher blood glucose such as hyperlipidaemia via inhibition of liver x receptors signaling pathway, modulation of transcription factors such as activation of peroxisome proliferator-activated receptors and modulation of rate limiting enzymes of carbohydrate metabolism [23,24] , garlic and citrus extract contain flavonoids which have anti-diabetic effect through their ability to modulate glucose metabolism or insulin sensitivity at different levels, increase glucose uptake and insulin secretion, and inhibit glucose production [25] Also this results could be attributed to the antioxidant vitamins present in garlic and citrus extract . The mechanism of action could be explained through the ability of the antioxidant vitamins to scavenge free radicals preventing alloxan-induced oxidative stress and protecting the β cells. ...
Article
Full-text available
The current study was designated to investigate the effect of Allium sativum and Citrus aurantifolium plants (C. aurantifolium) extract on blood glucose and lipid profile as well as body weight in diabetic rats, thirty adult rats were divided into five groups (6rat for each). G1 :served as healthy control given tap water G2 :diabetic without treatment , G3: diabetic treated with garlic extract 150 mg\kg body weight, G4:diabetic treated with C. aurantifolium and G5: group treated with150 mg\kg mix extracts (garlic and C. aurantifolium).All treated animals were given orally 1 ml of extracts every day. The effects of aqueous extract of garlic and C. aurantifolium on some parameters were investigated in normal and diabetic rats such as fasting blood sugar(FBS), fasting serum insulin(F.serum insulin) ,ketone body , lipid profile (Cholesterol , Triglyceride, High density lipoprotein(HDL),and Low density lipoprotein LDL) , the results investigated a significant decrease in glucose levels in group treated with mix plants(159.73±2.67) as compared with garlic (176.10±2.69) and C. aurantifolium (205.45±4.09) after twenty days of treatment, also the results display a significant improvement in insulin level in groups which treated with garlic , C. aurantifolium and mix plants (4.61±1.22 ,3.69±1.03 and 4.21±1.50 mg\dl respectively) compared with untreated diabetic group (1.88±0. 60), the value of ketone body was decreased in all treated groups with garlic, C. aurantifolium and mix plants(5.73±1.98, 6.94±2.86 and4.90±1.84) respectively, the results report a significant decline in cholesterol level in groups treated with garlic ,C. aurantifolium and mix extract (91±3.98, 95±4.35 and 87±2.45)mg\dl respectively compared with the untreated diabetic group (108±3.08 mg\d). the level of Triglyceride reported a significant p<0.05 decrease in all groups treated with garlic ,C. aurantifolium and mix extract (89±3.96, 90±3.78 and 85±3.73) mg/dl respectively compared with untreated diabetic group (102±4.43) mg\dl. HDL level revealed significant p<0.05 improvement in groups treated with garlic ,C. aurantifolium and mix extract(38±2.94, 32±2.09 and 42±3.02) mg\dl compared with control and untreated diabetic groups (30±2.12 and 24±3.53) mg\dl , reduced level of LDL were assessed in groups treated with garlic ,C. aurantifolium and mix extract(40±3.59, 43±4.50 and30±3.42) mg\dl. There was a significant p<0.05 improvement in body weight in the group treated with mix plants extract (184 ±4.30 g) after 30 days as compared with these groups at the beginning of experiment (178 ±2.93) g.
... Inhibits a-glucosidase and prevents formation of advanced glycation endproduct Oleanolic acid Improves insulin response by preserving and enhancing functionality of b-cells; activation of the transcription factor Nrf2 (Castellano et al., 2013) Promote insulin signal transduction and inhibit insulin resistance (Wang et al., 2011) Inhibits glucose production and stimulates glucose utilization (Zhang et al., 2014) Linalool Enhances glucose uptake (More et al., 2014) Piperine Inhibits a-glucosidase (Kumar et al., 2013) PPAR-ƴ receptor agonist (Kharbanda et al., 2016) Capsaicin Inhibits a-glucosidase, aamylase, and tyrosinase (Nanok and Sansenya, 2020) Phenylpropanoids Stimulates insulin secretion (Krishnan et al., 2014) Limolene Regulates enzymes involved in carbohydrate metabolism, stimulates insulin secretion and prevents glycation of haemoglobin (Murali and Saravanan, 2012;Habtemariam, 2018) Phytol activation of nuclear receptors and heterodimerization of RXR with PPARc (Elmazar et al., 2013) b-caryophyllene insulinotropic and b cell regeneration (Basha and Sankaranarayanan, 2016;Kumawat and Kaur, 2020) L-chicoric acid Enhances insulin release and glucose uptake (Tousch et al., 2008) Vicenin-2 Inhibitsa-glucosidase, protein tyrosine phosphatase 1B (PTP1B), aldose reductase (RLAR), and prevents advanced glycation end products (AGE) ...
Article
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It is a chronic metabolic disorder of glucose metabolism, which is associated with an elevated level of glucose (hyperglycemia) in the blood. The unhealthy eating habit of people and irregular use of diabetes prescribed medications are one of the factors that have increased the prevalence of diabetes worldwide. However, the high cost of managing diabetes and adverse effects associated with the use of synthetic drugs has impelled the quest to search for cost-effective and safer alternative antidiabetic agents. Conversely, spices are added to food to improve their taste, color, flavor, and shelf-life; they also possess some therapeutic values including antidiabetic activity due to the presence of bioactive components. As a result, the present review focuses on some commonly used spices in Africa that have demonstrated antidiabetic activity in both in vitro and in vivo studies, thereafter, we highlighted some bioactive compounds in these spices and their possible mechanism of action.
... Monoterpenes, the major components of essential oils, are found in several citrus fruits (such as orange and lemon), cherry, mint, etc. They have been shown to have various health benefits, such as antioxidants, antidiabetics, anticancer and cholesterol-lowering effects (7)(8)(9). Previous studies have shown that myrtenal, a monoterpene contained in various food products such as cardamom, lemon, spearmint, pepper and mint, has antihyperglycemic, antioxidant, anticancer and immunostimulatory properties as well as acting as a potential inhibitor of acetylcholinesterase (10)(11)(12). ...
Article
The present study was undertaken to evaluate the chemopreventive activity of myrtenal, a natural monoterpene, against bladder carcinoma in rats induced with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) and promoted with γ-ionizing radiation (γ-IRR) as well as to assess the involvement of inflammation, apoptosis and oxidative damage in tumor development. Histopathological examination of rat bladder revealed the presence of noninvasive papillary transitional cell carcinoma (Grade 2) in sections from BBN group indicating the credibility of the applied carcinogenesis model. Myrtenal treatment caused improvement in urinary bladder mucosa with cells more likely in Grade 1. Administration of myrtenal to BBN-treated rats exhibited downregulation in the expressions of COX-2, NF-kB and STAT-3 associated with suppression of inflammatory cytokines levels of TNF-α and IL-6 as well as biomarkers of oxidative damage (MDA & NO). In addition, myrtenal treatment caused a significant increase in caspase-3 activity and Bax/Bcl-2 ratio. Data obtained suggested that the anti-inflammatory effect and the induction of apoptosis contributed largely to the beneficial antitumor effects of myrtenal in rats with BBN/γ-IRR-induced bladder carcinoma. Present findings, in addition to benefits described in other pathologies, indicated myrtenal as a potential adjuvant natural compound for the prevention of tumor progression of bladder cancer.
... Moreover garlic contain allicin , cysteine sulfoxide, and S-allyl cysteine sulfoxide and these compounds reduced the level of glucose by several mechanism that include, enhancing the secretion of insulin from beta cells, increasing the cell sensitivity to insulin and preventing the insulin activation caused by liver, the activity of allicin in reducing blood glucose in rats was similar to that investigated by insulin and glibenclamide. Garlic oil also was reported to decrease the serum alanine transferases ,amylase and aspartate in diabetic rats [22].The limonene effects include stimulation of insulin secretion ,regeneration of β-ells, amelioration of secondary complications of higher blood glucose such as hyperlipidaemia via inhibition of liver x receptors signaling pathway, modulation of transcription factors such as activation of peroxisome proliferator-activated receptors and modulation of rate limiting enzymes of carbohydrate metabolism [23,24] , garlic and citrus extract contain flavonoids which have anti-diabetic effect through their ability to modulate glucose metabolism or insulin sensitivity at different levels, increase glucose uptake and insulin secretion, and inhibit glucose production [25] Also this results could be attributed to the antioxidant vitamins present in garlic and citrus extract . The mechanism of action could be explained through the ability of the antioxidant vitamins to scavenge free radicals preventing alloxan-induced oxidative stress and protecting the β cells. ...
Article
Full-text available
The current study was designated to investigate the effect of Allium sativum and Citrus aurantifolium plants (C. aurantifolium) extract on blood glucose and lipid profile as well as body weight in diabetic rats, thirty adult rats were divided into five groups (6rat for each). G1 :served as healthy control given tap water G2 :diabetic without treatment, G3: diabetic treated with garlic extract 150 mg\kg body weight, G4:diabetic treated with C. aurantifolium and G5: group treated with150 mg\kg mix extracts (garlic and C. aurantifolium).All treated animals were given orally 1 ml of extracts every day. The effects of aqueous extract of garlic and C. aurantifolium on some parameters were investigated in normal and diabetic rats such as fasting blood sugar(FBS), fasting serum insulin(F.serum insulin) ,ketone body , lipid profile (Cholesterol , Triglyceride, High density lipoprotein(HDL),and Low density lipoprotein LDL) , the results investigated a significant decrease in glucose levels in group treated with mix plants(159.73±2.67) as compared with garlic (176.10±2.69) and C. aurantifolium (205.45±4.09) after twenty days of treatment, also the results display a significant improvement in insulin level in groups which treated with garlic , C. aurantifolium and mix plants (4.61±1.22 ,3.69±1.03 and 4.21±1.50 mg\dl respectively) compared with untreated diabetic group (1.88±0. 60), the value of ketone body was decreased in all treated groups with garlic, C. aurantifolium and mix plants(5.73±1.98, 6.94±2.86 and4.90±1.84) respectively, the results report a significant decline in cholesterol level in groups treated with garlic ,C. aurantifolium and mix extract (91±3.98, 95±4.35 and 87±2.45)mg\dl respectively compared with the untreated diabetic group (108±3.08 mg\d). the level of Triglyceride reported a significant p<0.05 decrease in all groups treated with garlic ,C. aurantifolium and mix extract (89±3.96, 90±3.78 and 85±3.73) mg/dl respectively compared with untreated diabetic group (102±4.43) mg\dl. HDL level revealed significant p<0.05 improvement in groups treated with garlic ,C. aurantifolium and mix extract(38±2.94, 32±2.09 and 42±3.02) mg\dl compared with control and untreated diabetic groups (30±2.12 and 24±3.53) mg\dl , reduced level of LDL were assessed in groups treated with garlic ,C. aurantifolium and mix extract(40±3.59, 43±4.50 and30±3.42) mg\dl. There was a significant p<0.05 improvement in body weight in the group treated with mix plants extract (184 ±4.30 g) after 30 days as compared with these groups at the beginning of experiment (178 ±2.93) g.
... Chuffa et al. (2014) reported that flavonoid compounds improve glycemic levels and lipid profile in rats fed with a hyper-caloric diet. Alkaloids and triterpenoids could reduce blood sugar by increasing insulin secretion from pancreatic beta cells (Murali and Saravanan, 2012;Ponnulakshmi et al., 2019). On the other hand, flavonoids help in glucose uptake by peripheral tissues (Cazarolli et al., 2008). ...
... Several studies focused on the evaluation of the anti-diabetic properties of this monocyclic monoterpene. Murali and Saravanan, (2012) administered increasing doses (50, 100 and 200 mg/kg b.w.) of limonene daily for 45 days in STZ-induced diabetic rats. The results showed an increase in liver glycogen with a decrease in plasma glucose and HbA1c levels along with a suppression in the activities of gluconeogenic enzymes (G6Pase and FBPase). ...
Article
Background Moroccan flora is rich with medicinal plants that are widely used in traditional medicine for the treatment of various diseases including diabetes. These plants possess several classes of bioactive molecules, which belong to different chemical families such as phenolic acids, flavonoids, terpenoids and alkaloids. Scope and approach This review highlights the published reports on the antidiabetic properties of Moroccan medicinal plants. The mechanism of action of these plants and their secondary metabolites were discussed in detail. Clinical trials on the antidiabetic active constituents were summarized demonstrating the potential application of these natural treasures to be developed as potent antidiabetic agents. Key findings and conclusions were reported to be used in the treatment of diabetes in Morocco. Among these medicinal plants, the antidiabetic activity was evaluated for 15 species in vitro and 30 species in vivo. The in vitro studies showed significant inhibition of enzymes involved in the intestinal metabolism of carbohydrates. The in vivo reports revealed that the extracts and essential oils of these plants exhibited several antidiabetic effects such as a decrease of blood glucose and an increase of insulin secretion. Phytochemical analysis of the active plants revealed the presence of 148 secondary metabolites. These compounds belong to different chemical classes such as terpenoids, flavonoids, alkaloids, phenolic acids, and fatty acids. Among the identified compounds, 95 were evaluated for their antidiabetic activity. The results showed that these compounds manage diabetes by several mechanisms such as enzymatic inhibition, interference with glucose and lipid metabolism signaling pathways, and the inhibition and/or the activation of gene expression involved in glucose homeostasis. Eighteen active compounds reached clinical trials and showed impressive results in controlling diabetes and its manifestations.
... 19 Limonene (triterpenoid) causes the stimulation of insulin secretion due to the regenerated cell, lower the blood glucose, and modulate the critical enzymes of carbohydrate metabolism (increased glycolysis and decreased gluconeogenesis). 20 Tannic acid causes a lowering of blood glucose levels. It enhances the glucose utilization by inducing glucose transporters and through activation of insulin-mediated signaling pathways. ...
Article
Diabetes is a chronic metabolic disorder characterized by a high blood glucose concentration, i.e., hyperglycemia or caused by insulin deficiency, often combined with insulin resistance. In the Present study, the antidiabetic and antioxidant activity of the methanolic extract of Tagetes patula flower heads was screened out in rodent models. The pharmacological evaluation was carried out using 200 and 400 mg/kg, b.w. The in-vivo antidiabetic activity was performed in streptozotocin, dexamethasone-induced diabetic models and oral glucose tolerance test. Metformin hydrochloride was used as a standard. The parameters like blood glucose levels, insulin levels, homeostasis assessment of insulin resistance, insulin sensitivity, and fasting glucose-insulin ratio were estimated in these models. The in-vitro antioxidant activity of methanolic extract of Tagetes patula was performed by using hydroxyl radical scavenging assay and Ascorbic acid was used as a standard. The preliminary phytochemical screening of Tagetes patula revealed the presence of phytoconstituents like alkaloids, flavonoids, saponins, steroids, phenols, carbohydrates, triterpenoids, and tannins. The extract showed a significant decrease in the elevated blood glucose levels in streptozotocin, dexamethasone-induced diabetic models, and also in the oral glucose tolerance test. The extract prevented insulin resistance and significantly increased insulin sensitivity in the dexamethasone-induced model. The various phytochemical constituents like alkaloids, flavonoids, saponins, steroids, and phenols might be responsible for lowering the blood glucose levels in the animal models mentioned above. The extract showed significant scavenging activity against hydroxyl free radicals. From the above outcomes, it is flawless that the methanolic extract of Tagetes patula has antidiabetic and antioxidant activities.
... On the contrary, D-limonene inhibited liver glycogen as well as the activity of the glycolytic enzyme glucokinase in diabetic rats. Such antidiabetic effects were proportional with glibenclamide [136]. These findings support the potential antihyperglycemic activity of D-limonene reported in the literature. ...
Article
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Diabetes mellitus (DM) is a chronic metabolic condition characterized by persistent hyperglycemia due to insufficient insulin levels or insulin resistance. Despite the availability of several oral and injectable hypoglycemic agents, their use is associated with a wide range of side effects. Monoterpenes are compounds extracted from different plants including herbs, vegetables, and fruits and they contribute to their aroma and flavor. Based on their chemical structure, monoterpenes are classified into acyclic, monocyclic, and bicyclic monoterpenes. They have been found to exhibit numerous biological and medicinal effects such as antipruritic, antioxidant, anti-inflammatory, and analgesic activities. Therefore, monoterpenes emerged as promising molecules that can be used therapeutically to treat a vast range of diseases. Additionally, monoterpenes were found to modulate enzymes and proteins that contribute to insulin resistance and other pathological events caused by DM. In this review, we highlight the different mechanisms by which monoterpenes can be used in the pharmacological intervention of DM via the alteration of certain enzymes, proteins, and pathways involved in the pathophysiology of DM. Based on the fact that monoterpenes have multiple mechanisms of action on different targets in in vitro and in vivo studies, they can be considered as lead compounds for developing effective hypoglycemic agents. Incorporating these compounds in clinical trials is needed to investigate their actions in diabetic patients in order to confirm their ability in controlling hyperglycemia.
... verbenaca that has been shown to improve glucose homeostasis. Indeed, this substance boosts hepatic glycogen and plasma glucose levels [72] (Figure 8). ...
Article
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The family Lamiaceae contains several plants used in traditional medicine to fight against different diseases. Salvia verbenaca L. (S. verbenaca) is one of the Lamiaceae species distributed around the Mediterranean regions. This plant exhibits different bioactive properties, including antibacterial, anticancer, antioxidant, antileishmanial, antidiabetic, immunomodulatory, and wound healing. This review was conducted to revise previous studies on S. verbenaca addressing its botanical description, geographical distribution, and phytochemical, pharmacological, and toxicological properties. Moreover, the main pharmacological actions of S. verbenaca major compounds were well investigated. Literature reports have revealed that S. verbenaca possesses a pivotal role in medicinal applications. The findings of this work noted that S. verbenaca was found to be rich in chemical compound classes such as terpenoids, phenolics, fatty acids, sterols, and flavonoids. Numerous studies have found that S. verbenaca essential oils and extracts have a wide range of biological effects. These results support the potential pharmacological properties of S. verbenaca and its traditional uses. This analysis can constitute a scientific basis for further refined studies on its pure secondary metabolites. Therefore, the outcome of the present work may support the perspective of identifying new therapeutical applications with detailed pharmacological mechanisms of S. verbenaca to prevent the development of some diseases such as neurodegenerative disorders. However, toxicological investigations into S. verbenaca are needed to assess any potential toxicity before it can be further used in clinical studies.
... The oils were not as active as acarbose (IC 50 of 6.21 μg/mL) that was used as standard, but the oil from the dry season harvest was more active than the oil from rainy season harvest. Earlier work revealed that D-limonene had antihyperglycemic property against treptozotocininduced diabetic rats [29][30][31] . Thus, the higher antidiabetic activity of the oil from dry season harvest is attributable to the abundant of Dlimonene in the oil. ...
Article
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This study investigated the effect of seasonal variation on the chemical composition, antioxidant and antidiabetic activities of essential oil from leaves of Eucalyptus globulus. Pulverized leaves (500 g) of E. globulus from dry and rainy season harvests afforded 0.54 and 0.43 % (w/w) of essential oils respectively when subjected to hydrodistillation. GC and GC/MS analyses revealed the presence of forty-five and thirty-three compounds that represented 95.4 and 98.4 % of the oils obtained from leaves harvested during the dry and rainy seasons. The principal constituents of the essential oils were; D-limonene, m-cymene, o-cymene, 6-camphenol, terpinen-4-ol, globulol, diosphenol and spathulenol. The oils showed scavenging activity for DPPH radical with IC50 of 20.15 (dry) and 11.23 μL/mL (rainy). The essential oils showed significant reducing powers of 356.46±0.88 (dry) and 394.34±0.95 (rainy) FRAP equivalent. The oils inhibited the activity of α-amylase with IC50 of 8.37 (dry) and 6.78 (rainy) μg/mL. The IC50 for the α-glucosidase inhibition of the oils were 6.19 (dry) and 7.20 (rainy) μg/mL. The antioxidant and antidiabetic activities of the oils compared favourably with the standards used for the study. Hence, the essential oils can serve as an alternative to synthetic drugs to ameliorate oxidative stress and management of type 2 diabetes.
... The antidiabetic effect of D-limonene was comparable with glibenclamide (600 μg/ kg bw) treated diabetic group. Therefore, D-limonene mitigates hyperglycemia through regulation of carbohydrate metabolism-related genes in diabetic rats (Murari and Saravanan 2012). ...
Chapter
The increased worldwide prevalence of pre-diabetes and diabetes, especially type 2 diabetes, requiring different strategies for their prevention and management. A new focus is the reversal of diabetes dysbiosis, a disruption of gut microbiota homeostasis, which is closely related to elevated blood glucose levels and altered metabolic parameters. In this sense, a balanced diet plays a key role, and, particularly, probiotic and prebiotic have shown a promising role. This chapter explored current knowledge on the potential of probiotic and prebiotic to modulate glucose homeostasis. We showed that the consumption of probiotics and prebiotics is a promising strategy with a beneficial impact on gut microbiota and glycemic control. Furthermore, specific probiotic strains, such as L. acidophilus, L. casei strain Shirota, and B. lactis Bb12, have demonstrated the ability to improve parameters related to pre-diabetes and type 2 diabetes. In addition, polyphenols are emerging as a new alternative in glycemic control through the production of short chain fat acids (SCFA) and decreased lipopolysaccharides (LPS) translocation that leads to metabolic endotoxemia. Finally, the ingestion of beneficial bacteria, and foods rich in fiber and polyphenols, or a combination of them, is a good strategy for the control of pre-diabetes and type 2 diabetes, but more studies are still needed, mainly clinical trials, for these strategies are improved and widely used.
... The antidiabetic effect of D-limonene was comparable with glibenclamide (600 μg/ kg bw) treated diabetic group. Therefore, D-limonene mitigates hyperglycemia through regulation of carbohydrate metabolism-related genes in diabetic rats (Murari and Saravanan 2012). ...
Chapter
Pre-diabetes is a stage that usually precedes the onset of type 2 diabetes with a slight increase in fasting glucose, between 5.6 and 6.9 mmol/L; decreased glucose tolerance, between 7.8 and 11 mmol/L; and glycated hemoglobin, between 5.5 and 6.4% (ADA 2020). These biochemical abnormalities are usually caused by defects in insulin secretion from pancreatic cells, low insulin activity, or both (Unwin et al. 2002). Pre-diabetes can eventually lead to type 2 diabetes, which is characterized by hyperglycemia due to the inability of cells to respond fully to insulin, or to be resistant to insulin. Insulin resistance is characterized by insulin inefficiency in promoting glucose uptake by tissues and low intracellular glucose concentration signals for increased insulin production by the pancreas. Over time, depleted pancreatic beta cells reduce or stop insulin production, further elevating blood glucose levels (>6.9 mmol/L), characteristic of the diabetes condition. According to epidemiological data, type 2 diabetes is common in the elderly, but its frequency has increased in children and young adults due to high rates of obesity, sedentary lifestyle, and unbalanced diet, with excess fat and sugar. All of these factors indicate that both type 1 and type 2 diabetes result from a combination of genetic predisposition and environmental triggers (IDF 2020). Type 2 diabetes symptoms are similar to those of type 1 diabetes, but they are difficult to be identified in the early stages due to the long pre-diagnosis process, and, therefore, up to one third of the population may not be diagnosed early (Bansal 2015; Kaur 2014; Buchanan et al. 2002). This can be detrimental for a favorable prognosis after a long period of latent disease, and complications such as retinopathy or ulcers in the lower limbs that do not heal may occur (Chiasson et al. 2002). Furthermore,visceral obesity common in overweight and obese patients is related to the local and systemic inflammatory process, closely linked to the development of these comorbidities (ADA 2020). Regarding the healthy population, individuals with pre-diabetes and diabetes have a higher risk over the time of developing cardiovascular disease, metabolic syndrome, and polycystic ovaries, in addition to higher morbidity and mortality rates (Bansal 2015; Kaur 2014). Considering the close relationship between pre-diabetes, obesity, and diet, it is important to examine the influence of intestinal microbiota in this context. Intestinal microbiota is characterized by a diverse community of bacteria responsible for influencing nutrient metabolism, immune responses, and resistance to infectious pathogens (Nicholson et al. 2012; Belkaid and Hand 2014; van Nood et al. 2013). In the diabetic population, the intestinal microbiota presents a pattern of dysbiosis, which can be the starting point for the evolution of pre-diabetes to type 2 diabetes and other chronic diseases (Pratley 2013; Ziemer et al. 2008; Tsui et al. 2008; Stefanakia et al. 2018). Current scientific evidence has shown that probiotics or prebiotics, including phenolic compounds, can play a widely recognized role in the regulation of the intestinal microbiota, altering microbial composition and the metabolism of the bacteria and host (Tsai et al. 2019; Wang et al. 2020). Based on these fundamentals, this chapter will address the intrinsic relationships between the consumption of probiotics and prebiotics in individuals with pre-diabetes and type 2 diabetes.
... Another constituent, limonene, has strong antimetabolic activity as an anticancerous and antidiabetic agent. d-Limonene showed activity as an antidiabetic agent by reducing the level of plasma glucose, glycosylated hemoglobin levels, and activity of gluconeogenic enzymes and increasing glucokinase activity and liver glycogen level [45]. It was confirmed that d-limonene not only decreases the white and brown adipocytes, serum triglycerides, and glucose levels in the blood of the obese mice but also inhibits lipid accumulation in the liver. ...
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Background: The metabolic syndrome increases the risk of different diseases such as type 2 diabetes. The prevalence of metabolic syndrome has rapidly grown and affected more than 230 million people worldwide. Viola odorata is a traditionally used plant for the treatment of diabetes; however, its mechanism to manage diabetes is still unknown. Purpose: This study was designed to systematically assess the mechanism of action of Viola odorata in diabetes. Methods: An extensive literature search was made to establish an ingredient-target database of Viola odorata. Of these, targets related to diabetes were identified and used to develop a protein-protein interaction network (PPIN) by utilizing the STITCH database. The obtained PPIN was assessed through Gene Ontology (GO) enrichment analysis based on ClueGO plugin. Results: According to the acquired data, there were about 143 chemical constituents present in Viola odorata having 119 protein targets. Of these, 31 targets were established to give the pharmacological effect against diabetes. The UniProt database was used for screening of 31 targets, out of which Homo sapiens contained 22 targets. Ultimately, 207 GO terms, grouped into 41 clusters, were found by gene analysis, and most of them were found to be linked with diabetes. According to findings, several proteins including TP53, BCL2, CDKN1A, 1L6, CCND1, CDKN2A, and RB1 have a significant role in the treatment of diabetes by Viola odorata. Conclusion: The possible activity of Viola odorata in the management of diabetes may be mediated by several molecular mechanisms, including the glutamine metabolic process, IRE1-mediated unfolded protein response, and pentose metabolic process.
... Dose dependent antidiabetic activity was observed by them when studied in alloxan-induced diabetic Wistar rats. Phytocompounds like camphene (Hachlafi et al., 2021), camphor (Drikvandi et al., 2020), geraniol (Babukumar et al., 2017), and limonene (Murali and Saravanan, 2012) may be responsible for such antidiabetic property of Alternanthera pungens Kunth. ...
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Ethnopharmacological relevance: The genus Alternanthera ( Amaranthaceae ) comprises 139 species including 14 species used traditionally for the treatment of various ailments such as hypertension, pain, inflammation, diabetes, cancer, microbial and mental disorders. Aim of the review: To search research gaps through critical assessment of pharmacological activities not performed to validate traditional claims of various species of Alternanthera. This review will aid natural product researchers in identifying Alternanthera species with therapeutic potential for future investigation. Materials and methods: Scattered raw data on ethnopharmacological, morphological, phytochemical, pharmacological, toxicological, and clinical studies of various species of the genus Alternanthera have been compiled utilizing search engines like SciFinder, Google Scholar, PubMed, Science Direct, and Open J-Gate for 100 years up to April 2021. Results: Few species of Alternanthera genus have been exhaustively investigated phytochemically, and about 129 chemical constituents related to different classes such as flavonoids, steroids, saponins, alkaloids, triterpenoids, glycosides, and phenolic compounds have been isolated from 9 species. Anticancer, antioxidant, antibacterial, CNS depressive, antidiabetic, analgesic, anti-inflammatory, and immunomodulator effects have been explored in the twelve species of the genus. A toxicity study has been conducted on 3 species and a clinical study on 2 species. Conclusions: The available literature on pharmacological studies of Alternanthera species reveals that few species have been selected based on ethnobotanical surveys for scientific validation of their traditional claims. But most of these studies have been conducted on uncharacterized and non-standardized crude extracts. A roadmap of research needs to be developed for the isolation of new bioactive compounds from Alternanthera species, which can emerge out as clinically potential medicines.
... Moreover, scientifically proven studies confirm that contents of lemon fruits accelerate the regeneration of wounds in diabetics. (Murali and Saravanan, 2012). In addition, studies have shown that the essential oil extracted from lemon fruits has a significant anti-inflammatory effect (Amorim et al. 2016), an anti-allergic effect (Tsujiyama et al. 2013) and slimming properties by reducing body weight and body fat mass (Kim et al. 2015). ...
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Lemon trees (Citrus lemon L.) are among the trees scattered in Southeast Asia, especially Malaysia, The importance of lemons has increased in recent times, especially after the spread of the Covid-19 epidemic around the world, as lemon juice rich in vitamin C is fortified for the immunity of the human body. Also, it is an important source of Flavonoids, known as antioxidants, which remove free radicals that damage tissue cells within the body. Bio-fertilizers are products containing multiple genera of microorganisms in large numbers and beneficial to both plants and soil in an integrated manner. In addition bio-fertilizers have proved that increase the nutrient content inside plants, whether in leaves or fruits,which is reflected in the quantity and quality of fruits and also balance the ratio between plant nutrients in the soil. This review discussed the nutritional and health benefits of lemon and the importance of bio-fertilizer on fruit growth, yield and fruit quality of lemon.
... It can also reduce blood glucose. In this way, it can prevent from diabetes (D-limonene) [18]. ...
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Lemon is an important plant, which on the bases of its biological activities, used for medicine belongs to Rutaceae family and also known as a medicinal plant. Essential oils and other compounds present in lemon juice are at the main interest of biologists because of their various functionals. Lemon juice is the product of natural origin can be use as an alternative to synthesis products and play a vital role because of its biological activities. The results obtained from many studies reveal that the biological potentials of essential oil and other compounds of C. limon are probably due to the particular chemical composition of lemon juice mainly the high amounts of vitamin C. Therefore, this essential components could be used for various purposes based on their biological activities. The aim of this review article is to explore the vital importance of vitamin C and constituents of lemon juice and to evaluate its biological activities.
... A hypothesis for the possible mechanism of hypoglycemic activity of this plant may be during its main bioactive compounds. The hypoglycemic impact of limonene has been previously reported in diabetic rats by decreasing gluconeogenic enzymes' activities, increasing the glycolytic enzymes, and stimulating insulin secretion in pancreatic β-cells [59,60]. Cumin aldehyde in the Bunium Persicum oilseeds has significant inhibitory activity against the α-glucosidase enzyme that catalyzes the final step in the digestive process of carbohydrates. ...
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Background: Diabetes mellitus is the most common metabolic disorder worldwide. We aimed to determine the metabolic and clinical responses to Bunium Persicum (Black Caraway) supplementation in overweight and obese patients with T2DM. Methods: Participant recruitment took place in the diabetic clinic of Bu-Ali hospital in Zahedan. Due to the eligibility criteria, 60 participants were randomly placed into two groups, namely placebo (n = 30) and BP (n = 30). The supplementation was considered one 1000 mg capsule 2 times /day BP by meals (lunch and dinner) for 8 weeks. Physical activity levels, dietary intakes, anthropometric measurements [weight, height, and waist circumference], glycemic indices [fasting blood glucose (FBG) and insulin (FBI)], blood lipids [triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c)], and serum nesfatin-1 level were determined. Homeostasis model assessment-insulin resistance (HOMA-IR), Quantitative insulin sensitivity checks index (QUICKI), and Body Mass Index (BMI) were computed. Results: In comparison with placebo, BP significantly decreased FBG, HOMA-IR, and BMI (P < 0.05). The differences in the FBI, QUICKI, TG, TC, LDL, HDL, WC, and Nesfatin-1 were not significant (P > 0.05). Conclusion: BP supplementation improved serum glucose indices and BMI among overweight and obese T2DM patients. Further trials are needed to confirm results. Trial registration: Iranian Registry of Clinical Trials (IRCT), IRCT20181207041876N1, Registered 18/01/2019, https://irct.ir/trial/35752.
... This effect was comparable to that of the antidiabetic acarbose. Although limonene has been reported to show antidiabetic activity [13,14], this compound might not be responsible for the inhibition of -glucosidase even though it exists in high content in the inactive samples (CAO, CGO, CSO, CRO, and CMO). -Terpinene content was 1.7-fold higher in CMSO than in CAO suggesting that this monoterpene might contribute to theglucosidase inhibitory activity. ...
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Background. Inhibition of α-glucosidase is an important factor to control postprandial hyperglycemia in type 2 diabetes mellitus. Citrus essential oils (CEO) are among the most widely used essential oils, and some of them exhibited promising antidiabetic effect. However, the α-glucosidase inhibition of CEO has not been investigated so far. The present work aims to evaluate the α-glucosidase inhibition of essential oils from six Vietnamese Citrus peels. Methods. The chemical composition of essential oils obtained by hydrodistillation from six Citrus peels was analyzed by GC-MS. All essential oils were tested for their inhibitory activity on α-glucosidase using p-nitrophenyl-α-D-glucopyranoside as substrate. Results. In Buddha’s hand and lime peels, the major components were limonene (59.0–61.31%) and γ-terpinene (13.98–23.84%) while limonene (90.95–95.74%) was most abundant in pomelo, orange, tangerine, and calamondin peels. Among the essential oils, the Buddha’s hand oil showed the most significant α-glucosidase inhibitory effect with the IC50 value of 412.2 μg/mL. The combination of the Buddha’s hand essential oil and the antidiabetic drug acarbose increased the inhibitory effect. Conclusions. The results suggested the potential use of Buddha’s hand essential oil as an alternative in treatment of type 2 diabetes mellitus.
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D‐limonene or 4‐isopropenyl‐1‐methylcyclohexene (C10H16) is a monocyclic monoterpene abundant in citrus plants like lemon, orange, and grape. The application of D‐limonene in the form of flavor and fragrance additive in perfumes, soaps, foods, and beverages is consistently increased due to its high‐quality fragrance property. This review is intended to analyze and delineate every possible available evidence and details about D‐limonene with the special focus on its therapeutic efficacy. Many studies have reported that D‐limonene effectively plays a valuable role in the prevention of several chronic and degenerative diseases. This review provides worthy information about the beneficial effects of D‐limonene such as antioxidant, antidiabetic, anticancer, anti‐inflammatory, cardioprotective, gastroprotective, hepatoprotective, immune modulatory, anti‐fibrotic, anti‐genotoxic etc. This could in turn help in the application of D‐limonene for clinical studies. Practical implications Various plant families contain Terpenes as their secondary metabolites. Monoterpenes constitute an important part of these secondary metabolites. D‐limonene is a well‐identified monoterpene that is commonly applied as a fragrance ingredient in essential oils. D‐limonene is known to possess remarkable biological activities. It can be effectively used for treating various ailments and diseases. Due to its diverse functions, it can be efficiently utilized for human health.
Chapter
Terpenoids are volatile compounds synthetized and secreted by several organisms, in particularly by medicinal plants as secondary metabolites. These phytochemical compounds have shown several benefits in healthcare by their numerous pharmacological properties. Indeed, they have antibacterial, antifungal, antioxidant, antiviral, anticancer, and antidiabetic effects. Biological activities of terpenoids are related to their capacity to exert several mechanism insights. In this chapter, the pharmacological activities of terpenoids and their mechanism insights were explored and discussed.
Article
The influence of solvent polarity for hydroethanol (a), chloroform (b), and carbon tetrachloride (c) on bioactive extraction contents of Portulaca oleracea (II) and Achillea eriophora DC (III) were evaluated by GC-MS analysis. The antidiabetic and antilipidemic properties of different extracts were investigated on streptozotocine-induced diabetic rats and compared to glibenclamide as well-known chemical drug for the treatment of diabetes. The results indicated that extracts IIa – IIIc, IIIa, and IIIb reduced blood serum glucose significantly on days 9 and especially 16 after the induction of diabetes. In addition, LDL cholesterol level was reduced markedly by using IIb, IIc and IIIc extracts. Serum cholesterol and TG were significantly decreased (especially by carbon tetrachloride and chloroform extracts) in IIc and IIIc animal groups compared to control and glibenclamide groups. These results can be related to more extracted sterols, fatty acids, polyols (or alcohols), phenols and flavonoids as well as antraquinones and terpenes by polar or non-polar organic solvents compared to aqueous extracts of these medicinal herbs.
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Limonene is a monoterpene confined to the family of Rutaceae, showing several biological properties such as antioxidant, anti-inflammatory, anticancer, antinociceptive and gastroprotective characteristics. Recently, there is notable interest in investigating the pharmacological effects of limonene in various chronic diseases due to its mitigating effect on oxidative stress and inflammation and regulating apoptotic cell death. There are several available studies demonstrating the neuroprotective role of limonene in neurodegenerative diseases, including Alzheimer’s disease, multiple sclerosis, epilepsy, anxiety, and stroke. The high abundance of limonene in nature, its safety profile, and various mechanisms of action make this monoterpene a favorable molecule to be developed as a nutraceutical for preventive purposes and as an alternative agent or adjuvant to modern therapeutic drugs in curbing the onset and progression of neurodegenerative diseases. This manuscript presents a comprehensive review of the available scientific literature discussing the pharmacological activities of limonene or plant products containing limonene which attribute to the protective and therapeutic ability in neurodegenerative disorders. This review has been compiled based on the existing published articles confined to limonene or limonene-containing natural products investigated for their neurotherapeutic or neuroprotective potential. All the articles available in English or the abstract in English were extracted from different databases that offer an access to diverse journals. These databases are PubMed, Scopus, Google Scholar, and Science Direct. Collectively, this review emphasizes the neuroprotective potential of limonene against neurodegenerative and other neuroinflammatory diseases. The available data are indicative of the nutritional use of products containing limonene and the pharmacological actions and mechanisms of limonene and may direct future preclinical and clinical studies for the development of limonene as an alternative or complementary phytomedicine. The pharmacophore can also provide a blueprint for further drug discovery using numerous drug discovery tools.
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Limonene is one of the most common terpenes found in nature and a primary bioactive compound of essential oils obtained from citrus fruit peels. Limonene is considered as generally recognized as safe (GRAS) in the Code of Federal Regulations. Owing to its lemon-like odor and rich flavor profile, it has been widely used as a flavoring and/or preserving agent in numerous food products. It can be applied in many types of beauty and household products, such as fresheners, soaps, perfumes, shampoos, hair conditioners, shower gels, cleaning products, detergents, and eco-friendly pesticides. In this chapter, biogenesis, physicochemical properties, distribution, extraction/purification, metabolism/bioavailability, and medicinal/pharmaceutical and food applications of limonene are described.
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Plants are incredibly significant in the lives of people around the world. People rely on plants to satisfy basic human needs like food, clothing, shelter, and health care. Because of a rising world population, increasing wages, and urbanization, these needs are growing rapidly. Of course, plants provide food directly and often feed livestock that is then eaten on their own. The value of plants is likely to become fairer among countries as world economies become more accessible and market-oriented through trade agreements such as those from the World Trade Organization. The socio-economic significance of such an understanding of plants is defined in this chapter by providing evidence of the multiple benefits of plant breeding in and beyond agriculture based on reproducible findings and scientific evidence for arable crops.
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Background Quality control (QC) of nutraceuticals has always been a challenging task due to their complex nature and wide sources of variability. As a green, fast, and nondestructive tool that requires no sample preparation, near infrared spectroscopy (NIRS) is increasingly employed in this field. Advances in NIRS instrumentation and interpretation posed for its increasing application in nutraceutical QC. Scope and Approach In this review, NIRS application in nutraceuticals QC with special emphasis on novel trends from targeted and untargeted approaches is presented. The targeted approach comprises applications made towards analysis of relevant metabolite classes in nutraceuticals while the untargeted approach comprises discrimination of geographical origin, cultivars, varieties and fingerprinting of nutraceuticals. The value of NIRS application and its novel trends in nutraceuticals QC are critically assessed disclosing advantages and limitations with emphasis on areas demanding future advancements. Key Findings and Conclusions NIRS and its novel trends are outstanding analytical tools compared to other spectroscopic tools for QC of nutraceuticals from targeted and untargeted viewpoints. The review manifests the value of complementing NIRS with other vibrational technique (MIR) or a totally different analytical platform. In addition, hyperspectral imaging and portable devices applications in nutraceutical QC are less explored with proposed suggestions to overcome current limitations presented. Spectral simulation and 2D-COS techniques require broader application to prompt their advantages in nutraceuticals QC.
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Recently available drugs of synthetic origin in management of obesity and diabetes are costly and not affordable by poor people and have potential adverse side effects, and thereby these cause serious other complications among many obese and diabetic patients. As a result, some of these drugs have been withdrawn from the market. For this reason, most of the leading pharmaceutical industries have paid their attention for discovery of potential natural compounds with low-cost and minimal adverse effects for treatment of obesity and diabetes as an alternative strategy. In the earlier chapter, we have discussed that a large variety of natural resources, namely, dietary fruits, vegetables, grains, plants, seaweeds, edible and medicinal mushrooms, marine fishes and cucumbers, and microorganisms, have potential anti-obesity and antidiabetic effects. Their bioactive phytochemicals having diverse skeletal structures and belonging to different chemical classes, such as flavonoids, simple phenolics, lignans, stilbenoids, curcuminoids, tannins, alkaloids, terpenoids, steroids, saponins, organosulfurs, thiosugars, and polysaccharides. A growing body of evidence demonstrates that these natural products have multiple targets of action for prevention and treatment of obesity and diabetes. Most of these natural components exhibit hypolipidemic, hypoglycemic, antioxidant, and anti-inflammatory activities for improvement of insulin resistance, insulin secretion, and insulin action in insulin-responsive tissues for amelioration of lipid and glucose metabolic disorders in cellular and vivo models of obesity and diabetes. In this chapter, we address the pharmacology of some phytochemicals having potent anti-obesity and antidiabetic activity and their major natural sources and molecular targets.
Article
Background: The cardiovascular crisis is advancing rapidly throughout the world. A large number of studies have shown that plant polyphenols affect major mechanisms involved in cardiovascular events through their action on the antioxidant system, signaling, and transcription pathways. D-limonene, a monocyclic monoterpene obtained from citrus fruits, is reported to possess many pharmacological activities. Methods: The experiment was designed to determine the protective effect of D-limonene against cardiac injury induced by CCl4 in Wistar rats. Rats were treated with two doses of D-limonene against cardiac injury induced by CCl4. Serum toxicity markers, cardiac toxicity biomarker enzymes, inflammatory mediators, anti-oxidant armory, lipid peroxidation, lipid profile, and histology were done. Results: CCl4 intoxication resulted in a substantial rise in FFA, TC, TG, PL, LDL, VLDL, and a reduction in HDL, restoring these changes with the administration of D-limonene at a dosage of 200 mg/kg. CCl4 administration also resulted in lipid oxidation and decreased antioxidant activity. At the same time, D-limonene at a dosage of 200 mg/kg body weight inhibited LPO and restored in vivo antioxidant components to normal. CCl4 intoxication also resulted in a significant increase in inflammatory markers like IL-6, TNF-α, high sensitivity Corticotropin Releasing Factor (Hs-CRF), and biomarkers of cardiac toxicity like alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase MB (CKMB), and Troponin I & troponin-t activities. D-limonene reversed all these changes to normal. Histology further confirmed our obtained results. Conclusion: These findings indicate that D-limonene can ameliorate cardiac injury at a 200 mg/kg body weight dosage. Henceforth, D-Limonene intervenes in mediating CCl4 induced toxicity by various signaling pathways. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
Chapter
Terpenes make up the largest class of chemical compounds known in living organisms, being also the most diverse from the chemical, structural and functional points of view, with more than 80000 compounds already known. Terpene classes can be divided into hemiterpenes, monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, triterpenes, tetraterpenes, and polyterpenes. Monoterpenes, are formed by two units of isoprene and present various chemical structures and biological activities. Monoterpenes being the main constituents of several essential oils from medicinal aromatic plants, this chapter focuses on the main and most current scientific information on dietary monoterpene's effects in vivo and their role in health. Anticancer, anti‐inflammatory, antidiabetic, antioxidant activities and the cardiovascular and antihypertensive effects of monoterpenes are discussed in more detail. Considering the non‐toxic character and the benefits associated with its consumption, research related to the discovery and proof of its biological effects has been increasingly encouraged, reinforcing the need to use natural compounds as health promoters.
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Huanglongbing (HLB) is a destructive citrus greening disease; no commercially applicable measures exist. ‘LB8‐9’ Sugar Belle® (SB), originally developed for the fresh market, is the most HLB‐tolerant cultivar among commercially available varieties. Due to the limited capacity of the fresh fruit market, there is a need to increase the demand for SB juice. Kombucha is a fermented tea beverage with black tea and sugar, and is considered a healthy drink with an increasing market. Therefore, we aim to study the potential of using SB juice in kombucha production. Regular (black tea with no citrus juice added), Hamlin (black tea with Hamlin juice added), and SB kombucha (black tea with SB juice added) were prepared and analyzed to observe the composition of aroma and taste compounds in the kombuchas. Aroma and taste compounds in the kombuchas were analyzed using gas chromatography–mass spectrometry/olfactometry and liquid chromatography–triple quadrupole mass spectrometry, respectively. For aroma compounds, SB kombucha was characterized by high concentrations of terpenes and their derivatives, which have mandarin‐like aroma characteristics and health benefits such as antidiabetic and antioxidant effects. For taste compounds, SB kombucha contained higher amount of fructose and organic acids, which have the potential to increase the intensity of sweetness and sourness, and flavonoids. This would support the potential benefits of using SB to make kombucha. This study provides valuable information about the aroma and taste compounds in SB kombucha and its potential health benefits, compared with regular and Hamlin kombucha. This experiment provided valuable information on the elevated aroma and taste compounds, their potential health benefits, and the changes of those compounds during kombucha fermentation in ‘LB8‐9’ Sugar Belle® kombucha, compared to regular and Hamlin kombucha. In the absence of an effective cure or therapy for HLB, this can be the first step for developing alternative citrus product to help the citrus industry mitigate the negative impacts from HLB.
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Pulverised rhizome of Curcuma longa on hydrodistillation, afforded oil in the yield of 1.24% v/w. The oil was investigated by GC and GC/MS. Hydrocarbon monoterpene (46.9 %) constituted bulk of the oil. The major constituents of the oil were, β – bisabolene (13.9 %), trans - ocimene (9.8 %), myrcene (7.6 %), 1, 8 - cineole (6.9 %), α - thujene (6.7 %) and thymol (6.4 %).
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Antidiabetic activity of Feronia limonia Fruit and Artocarpus heterophyllus Bark extracts used as edible medicine by local tribal population of Vellore districts were analyzed in streptozotocin induced diabetic rats. Breliminary phytochemical screening revealed the presence of high contents of flavonoid in methanolic extract of Feronia limonia and ethyl acetate extract of Artocarpus heterophyllus compared to other extracts. Diabetes was induced by single intraperitoneal injection of streptozotocin (45 mg kg -1). Diabetic rats were treated with these extracts at a dose of 200 and 400 mg kg -1 for 30 days. Hypoglycemic activities of extract treated diabetic rats were assessed by the percentage reduction in fasting blood glucose level. Feronia limonia extract showed significant (p<0.05) decrease in blood glucose level when compared to the Artocarpus heterophyllus extract. Treatment of these extracts also had significant decrease in serum cholesterol level and regain in body weight of diabetic rats. The results suggest that unique bioactive constituents responsible for improving type 2 diabetic rats are present and further has to be purified, isolated and characterized to contribute better therapy for NIDDM.
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Diabetes mellitus is defined as a group of metabolic diseases whose common feature is an elevated blood glucose level (hyperglycaemia). Chronic hyperglycaemia is associated with the long-term consequences of diabetes that include damage and dysfunction of the cardiovascular system, eyes, kidneys and nerves. The complications of diabetes are often divided into two groups: microvascular
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Thujone, which is the major constituent in Salvia sp. (Lamiaceae), was found to correct the lipid profile (cholesterol and triglycerides) in diabetic rats. Oral treatment with thujone (5 mg kg⁻¹ body weight dose) significantly adjusted cholesterol and triglyceride levels in diabetic rats (p ≤ 0.05) to normal levels compared to diabetic untreated rats. This provides a premise in the field of finding new agents to treat diabetic complications.
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Evaluation of hypoglycemic activity of methanolic stem bark extract of Adansonnia digitata in Wistar rats has beeninvestigated. Antidiabetic potentials of the plant extract at the doses of 100,200 and 400 mg/kg intraperitoneally administered onStreptozocin diabetes Wistar rats. Treatment of streptozocin diabetic Wistar rats with the extract caused a significant (P<0.05)reduction in the blood glucose levels when compared with control. The dose of 100mg/kg shown a significant decreased (p<0.05)after 1, 3 5 and 7 hours of extract administration when compared to control normal saline. Also the dose of 200 mg/kg shown asignificant decreased (p<0.05) after 3, 5 and 7 hours of extract administration. The dose of 400 mg/kg also shown a significantdecreased( p<0.05) after 5 and 7 hours of extract administration when compared to control normal saline. The highest activity residesat the dose of 100 mg/kg with percentage glycemic change of 51 % after 7 hours of extract administration while the other two doses200 and 400 mg/kg have glycemic change of 39% and 31% respectively after 7 hours of extract administration. The phytochemicalscreening revealed the presences of tannins, carbohydrate, terpenes, saponins, flavonoids and alkaloids. The median lethal dose (LD50) in mice was calculated to be 1264.9 mg/kg bodyweight. This result suggests that the methanolic stem bark of Adansonniadigitata possess antidiabetic effect on streptozocin induced diabetic Wistar rats.Industrial relevance: The herbal medicines are getting more importance in the treatment
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To investigate the poorly understood relationship between the process of urbanization and noncommunicable diseases (NCDs) through the application of a quantitative measure of urbanicity. We constructed a measure of the urban environment for seven areas using a seven-item scale based on data from the Census of India 2001 to develop an "urbanicity" scale. The scale was used in conjunction with data collected from 3705 participants in the World Health Organization's 2003 STEPwise risk factor surveillance survey in Tamil Nadu, India, to analyse the relationship between the urban environment and major NCD risk factors. Linear and logistic regression models were constructed examining the relationship between urbanicity and chronic disease risk. Among men, urbanicity was positively associated with smoking (odds ratio: 3.54; 95% confidence interval, CI: 2.4-5.1), body mass index (OR: 7.32; 95% CI: 4.0-13.6), blood pressure (OR: 1.92; 95% CI: 1.4-2.7) and low physical activity (OR: 3.26; 95% CI: 2.5-4.3). Among women, urbanicity was positively associated with low physical activity (OR: 4.13; 95% CI: 3.0-5.7) and high body mass index (OR: 6.48; 95% CI: 4.6-9.2). In both sexes urbanicity was positively associated with the mean number of servings of fruit and vegetables consumed per day (P < 0.05). Urbanicity is associated with the prevalence of several NCD risk factors in Tamil Nadu, India.
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Artemisia herba alba is widely used in Iraqi folk medicine for the treatment of diabetes mellitus. However, very few scientific and medical studies were carried out to assess the efficacy and toxicity of A. herba alba. In this study feeding diabetic rats and rabbits with 0.39 g/kg body weight of the aqueous extract of the aerial parts of the plant for 2-4 weeks shows a significant reduction in blood glucose level, prevents elevation of glycosylated haemoglobin level and possesses a hypoliposis effect, in addition to the protection against body weight loss of diabetic animals.
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Diabetes has been classified as a disease of glucose overproduction by tissues, mainly liver and glucose underutilization by insulin requiring tissues like liver, adipose and muscle due to lack of insulin. There is, however, glucose over utilization in tissues not dependent on insulin for glucose transport like kidney, nerve and brain. There are serious complications due to this excess glucose in these tissues and their reversal is important for a good metabolic control and normalisation of other parameters. Insulin, trace metals and some plant extracts have been used to see the reversal effects of the complications of diabetes in liver and kidney in experimental diabetes. Almost complete reversal of the metabolic changes has been achieved in the activities of key enzymes of metabolic pathways in liver and kidney and an effective glucose control has been achieved suggesting a combination of therapies in the treatment of metabolic disturbance of the diabetic state.
Article
Two common essential oil constituents, 1,8-cineole and limonene, were assessed for antimicrobial activity, using the minimum inhibitory concentration (MIC) microtitre plate method against eight organisms. The limonene enantiomers, i.e. (+), (−) and the racemate, singularly and in combination (1:1) with 1,8-cineole, were investigated to establish possible interactions. The MIC values were in the ranges 3–27 mg/ml for (+)-limonene; 2–27 mg/ml for (−)-limonene and 23 mg/ml for 1,8-cineole, depending on the pathogen studied. The combinations, when investigated in a 1:1 ratio, mostly indicated reduced activity. Using various ratios of limonene and 1,8-cineole, the specific interaction was further investigated against Staphylococcus aureus (Gram-positive), Pseudomonas aeruginosa (Gram-negative) and a yeast, Cryptococcus neoformans. A figurative representation of the results using isobologram construction indicated that, depending on the ratio and specific enantiomer, an additive, synergistic or antagonistic interaction may be observed. Copyright © 2007 John Wiley & Sons, Ltd.
Article
This chapter discusses the determination of glucose 6-phosphate dehydrogenase from erythrocytes. In the course of the assay method, the reduction of triphosphopyridine nucleotide+ (TPN+) to reduced triphosphopyridine nucleotide (TPNH) results in the appearance of an absorption band at 340 mμ. In the presence of saturating concentrations of G-6-P and TPN, the rate of change of absorbancy at this wavelength is proportional to the enzyme concentration. The assay is carried out at room temperature (25°). One unit of enzyme activity is defined as that quantity which catalyzes the reduction of micromole of TPN per minute under the above assay conditions. This corresponds to an absorbancy change of 2.07 per minute. Protein is measured by the optical method of Warburg and Christian or by the colormetric method of Lowry. Specific activity is defined as the units of enzyme per milligram of protein. Enzyme having a specific activity of 113 units per milligram appears homogeneous on free and starch gel electrophoresis. In the analytical ultracentrifuge, one major component comprising approximately 80% of the protein is observed. One minor peak, which is believed to represent the monomeric form, is also present. The purified native enzyme is stable in solution for several weeks at 0°, and for prolonged periods at –20°. It may also be kept in solution for several hours at 40° without appreciable loss of activity.
Article
The hypoglycemic and antioxidative effects of Morinda citrifolia fruit extract were evaluated in streptozotocin (STZ)-induced diabetic rats. The ethanolic extract of Morinda citrifolia fruit at a concentration of 300mg/kg body weight/rat/day was orally administered to STZ-induced diabetic rats for a period of 30days. The elevated levels of blood glucose, glycosylated hemoglobin, blood urea, and serum creatinine in the diabetic rats reverted back to near normal after treatment with the noni fruit extract. Similarly significant decrease in the levels of plasma insulin and hemoglobin were elevated to near normal after treatment with fruit extract, suggesting the antihyperglycemic effect of Morinda citrifolia fruit. Determination of thiobarbituric acid reactive substance (TBARS), hydroperoxides, and both enzymatic and nonenzymatic antioxidants evidenced the antioxidative potential of the extract of noni fruit, which in turn may be responsible for its hypoglycemic potential. Alterations observed in the activities of pathophysiological enzymes such as serum aspartate transaminase (AST), serum alanine transaminase (ALT), and serum alkaline phosphatase (ALP) in the serum of control and experimental groups of rats revealed the tissue protective nature of Morinda citrifolia fruits, and the results of all the biochemical parameters analyzed were comparable with glyclazide, the standard reference drug.
Article
The use of thujone, a monoterpene ketone often present in sage (Salvia officinalis L.) or wormwood (Artemisia absinthium L.), for the treatment of diabetes mellitus was recently suggested in a study published in this journal. Evidence was based on the findings obtained in a diabetic rat model. After oral treatment with thujone (5 mg/kg bodyweight (bw)/day for 28 days), the cholesterol and triglyceride levels were significantly adjusted to normal levels when compared to diabetic, untreated rats. While these results sound promising and worthy of further investigation, the well-defined profile of the adverse properties of thujone demands a cautious interpretation of these results. The therapeutic margin of thujone appears to be small, as a dose-related incidence of seizures was noted in 2-year National Toxicology Program studies in rats and mice. The dose level in the diabetic rat study is also considerably higher than a daily intake that is acceptable for humans (0.1 mg/kg bw/day).
Article
Salvia splendens (Labiatae) is widely used in Indian traditional medicine for the control of diabetes mellitus. In this study, the hypoglycemic effects produced by the acute and subacute administration of various extracts of S. splendens were investigated. Both the aqueous extract (SSAE) and the methanolic extract (SSME) from the aerial parts resulted in significant reductions of glycemia in streptozotocin (STZ)-induced diabetic rats after oral administration at a dose of 100 and 200 mg/kg, respectively. On oral administration, aqueous and methanolic extracts showed statistically significant (P < 0.001) effect by reducing the effect of glycemia in STZ-induced diabetic rats. These findings suggest the significant antihyperglycemic potential of the S. splendens extracts in ameliorating the diabetic conditions in diabetic rats. No significant effects were found in the normal rats.
Article
We estimated the number of people worldwide with diabetes for the years 2010 and 2030. Studies from 91 countries were used to calculate age- and sex-specific diabetes prevalences, which were applied to national population estimates, to determine national diabetes prevalences for all 216 countries for 2010 and 2030. Studies were identified using Medline, and contact with all national and regional International Diabetes Federation offices. Studies were included if diabetes prevalence was assessed using a population-based methodology, and was based on World Health Organization or American Diabetes Association diagnostic criteria for at least three separate age-groups within the 20-79 year range. Self-report or registry data were used if blood glucose assessment was not available. The world prevalence of diabetes among adults (aged 20-79 years) will be 6.4%, affecting 285 million adults, in 2010, and will increase to 7.7%, and 439 million adults by 2030. Between 2010 and 2030, there will be a 69% increase in numbers of adults with diabetes in developing countries and a 20% increase in developed countries. These predictions, based on a larger number of studies than previous estimates, indicate a growing burden of diabetes, particularly in developing countries.
Article
Limonene is a monoterpene present in citrus fruit and is used as flavouring agents of foods. It was shown that monoterpenes possess antioxidant activity. Previously, it was demonstrated that limonene exerts anti-proliferative action on a lymphoma cell line without modifying normal lymphocyte viability. H(2)O(2) has a modulator role in cell proliferation. In the present study, the effect of limonene on normal lymphocytes proliferation and its relation with H(2)O(2) level modulation was analysed, evaluating its effect on the activity of cell antioxidant enzymes, such as catalase, peroxidase and superoxide dismutase. Limonene exerted a biphasic effect on cell proliferation; the increase in cell proliferation was related to the decrease in H(2)O(2) level by the increase in catalase and peroxidase activities. Moreover, limonene protected the cells to the oxidative stress induced by exogenous addition of H(2)O(2). In view of these results, it is possible that limonene could protect normal lymphocytes from diseases related to oxidative stress, including cancer, but further research is necessary to establish the role of limonene as a potential antioxidant that can effectively protect lymphocytes from oxidative stress and mitochondrial dysfunction.
Article
Finger citron [Citrus medica L. var. Sarcodactylis Hort, Rutaceae] (FC) fruits, widely cultivated in Japan, the southern provinces of China and Taiwan, are commonly used as functional vegetables and preserved as sweetmeats. Previously we identified the major compounds in essential oils (% in EO) of FC fruits to be d-limonene (51.24), gamma-terpenene (33.71), alpha-pinene (3.40), and beta-pinene (2.88). Documented evidence on its insulin secretion characteristics is still lacking. In parallel to compositional analysis, we performed in vivo the safety, hypoglycemic, and antidiabetic tests in Sprague-Dawley-SPF rats and Wistar DIO rats respectively. By kinetic analysis on the hypoglycemic patterns of the intraperitoneal glucose tolerance (IPGTT) and the insulin-glucose tolerance tests (IGTT), its insulin secretagogue effect was confirmed. In conclusion, FC fruits that concomitantly possess insulin secretagogue and slimming effects would be very beneficial to type 2 diabetes mellitus patients.
Article
1. Net glycogen accumulation was measured in sequentially removed samples during perfusion of the liver of starved streptozotocin-diabetic rats, and shown to be significantly impaired, compared with rates in normal (starved) rats. 2. In perfusions of normal livers with glucose plus C3 substrates, there was an increase in the proportion of glycogen synthetase 'a', compared with that in the absence of substrates. This response to substrates, followed in sequential synthesis and enzymic sensitivity in the perfused liver of diabetic rats were reversed by pretreatment in vivo with glucose plus fructose, or insulin. Glucose alone did not produce this effect. 4. Glucose, fructose, insulin or cortisol added to e perfusion medium (in the absence of pretreatment in vivo) did not stimulate glycogen synthesis in diabetic rats. 5. In intact diabetic rats, there was a decline in rates of net hepatic glycogen accumulation, and the response of glycogen synthetase to substrates. The most rapid rates of synthesis were obtained after fructose administration. 6. These results demonstrate that there is a marked inherent impairment in hepatic glycogen synthesis in starved diabetic rats, which can be rapidly reversed in vivo but no in perfusion. Thus hepatic glycogen synthesis does not appear to be sensitive to either the short-term direct action of insulin (added alone to perfusions) of to long-term insulin deprivation in vivo. The regulatory roles of substrates, insulin and glycogen synthetase in hepatic glycogen accumulation are discussed.
Article
The monoterpene d-limonene has been shown to an effective, non-toxic chemopreventive agent in mammary and other rodent tumor models. The studies reported here investigated structure-activity relationships among limonene and three hydroxylated derivatives in the prevention of dimethyl-benz[a]anthracene (DMBA)-induced mammary cancer. Rats were fed control or 1% limonene, carveol, uroterpenol or sobrerol diets from 2 weeks before to one week after carcinogen administration. Carveol, uroterpenol and sobrerol significantly prolonged tumor latency and decreased tumor yield. Sobrerol was the most potent of the monoterpenes tested, decreasing tumor yield to half that of the control, a level previously achieved with 5% limonene diets. Excretion of radioactivity from [3H]DMBA was doubled in rats fed 5% limonene and nearly tripled in rats fed 1% sobrerol. Sobrerol is thus 5-fold more potent than limonene in both enhancing carcinogen excretion and in preventing tumor formation. These data demonstrate that hydroxylation of monoterpenes affects chemopreventive potential, with 2 hydroxyl groups > 1 > 0. Sobrerol, carveol and uroterpenol are novel cancer chemopreventive agents with little or no toxicity.
Article
The effect of alloxan induced diabetes on the dermal collagen content of albino rats was studied in relation to few lysosomal enzymes. Diabetes decreased the dermal collagen content. The specific activities of the lysosomal enzymes studied in the diabetic rat skin were elevated. It has been established that lysosomal enzymes degrade the connective tissue components. Thus, it may be suggested that the increase in the lysosomal enzymes studied should have facilitated the decrease in dermal collagen content of diabetic rats by increasing the degradation of dermal collagen.
Article
The effects of D-limonene and citrus fruit oils, i.e. orange oil and lemon oil, on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced neoplasia of the lungs and forestomach of female A/J mice were investigated. D-Limonene and the citrus fruit oils given p.o. 1 h prior to NNK, also administered p.o., inhibited pulmonary adenoma formation and the occurrence of forestomach tumors. In an additional experiment, D-limonene given p.o. 1 h prior to NNK administered i.p. again showed pronounced inhibition of pulmonary adenoma formation. This study provides additional data demonstrating that non-nutrient constituents of the diet can inhibit carcinogen-induced neoplasia when administered at a short time interval prior to carcinogen challenge.
Article
The effect of oral administration of sodium orthovanadate on hepatic malic enzyme (EC 1.1.1.40) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49) activities was investigated in nondiabetic and diabetic rats. Streptozotocin-induced diabetic rats were characterized by 4.7-fold increase in plasma glucose and 82% decrease in plasma insulin levels. The activities of hepatic malic enzyme and glucose-6-phosphate dehydrogenase were also diminished (P less than 0.001). Vanadate treatment in diabetic rats led to a significant decrease (P less than 0.001) in plasma glucose levels and to the normalization of enzyme activities, but it did not alter plasma insulin levels. In nondiabetic rats vanadate decreased the plasma insulin level by 64% without altering the enzyme activities. Significant correlation was observed between plasma insulin and hepatic lipogenic enzyme activities in untreated and vanadate-treated rats. Vanadate administration caused a shift to left in this correlation suggesting improvement in insulin sensitivity.
Article
Aconitan A did not affect plasma insulin levels in normal, glucose-loaded and alloxan-induced hyperglycemic mice and gave no influence on insulin binding to isolated adipocytes. Aconitan A exerted no effect on the activities of hepatic hexokinase, glucokinase, glucose-6-phosphatase and glucose-6-phosphate dehydrogenase, whereas it significantly increased hepatic phosphofructokinase activity. Although the activity of hepatic glycogen synthetase showed a tendency to increase, the activity of liver phosphorylase and glycogen content were unchanged by aconitan A. Aconitan A did not change the total cholesterol and triglyceride contents of plasma and liver.
Article
An enzyme-linked immunosorbent assay for the measurement of insulin in human serum has been developed. The test is based on the sandwich technique with two monoclonal antibodies directed against two different epitopes of insulin using coated plastic tubes as the solid phase and horse radish peroxidase as the label. The immunoreactions are completed in one step within 2 h. The horse radish peroxidase activity bound to the tube wall is measured photometrically after an additional 1-h incubation with the substrate. The standards used cover the range from 0 to 260 mU insulin/L. Employing the Enzymun-Test System ES 22 modular batch analyzer, the detection limit was found to be 3.7 mU insulin/L. Coefficients of variation (CV's) between 1.4-7.8% for intraassay precision and 5.6-10% for interassay precision were obtained over the concentration range of 17-107 mU Insulin/L. The correlation between the procedure described here (y) and a commercially available double antibody radioimmunoassay (x) is expressed by the following equation: y = 1.07x + 1.14 mU insulin/L.
Article
The relationship between the dose of intravenously administered streptozotocin (a N-nitroso derivative of glucosamine) and the diabetogenic response has been explored by use of the following indices of diabetogenic action: serum glucose, urine volume, and glycosuria, ketonuria, serum immunoreactive insulin (IRI), and pancreatic IRI content. Diabetogenic activity could be demonstrated between the doses of 25 and 100 mg/kg, all indices used showing some degree of correlation with the dose administered. Ketonuria was only seen with the largest dose, 100 mg/kg. The most striking and precise correlation was that between the dose and the pancreatic IRI content 24 hr after administration of the drug, and it is suggested that this represents a convenient test system either for both related and unrelated beta cytotoxic compounds or for screening for modifying agents or antidiabetic substances of a novel type. Ability to produce graded depletion of pancreatic IRI storage capacity led to an analysis of the relationship between pancreatic IRI content and deranged carbohydrate metabolism. Abnormal glucose tolerance and insulin response were seen when pancreatic IRI was depleted by about one-third, while fasting hyperglycemia and gross glycosuria occurred when the depletion had reached two-thirds and three-quarters, respectively. The mild yet persistent anomaly produced by the lowest effective streptozotocin dose, 25 mg/kg, exhibits characteristics resembling the state of chemical diabetes in humans and might thus warrant further study as a possible model. Finally, the loss of the diabetogenic action of streptozotocin by pretreatment with nicotinamide was confirmed and was shown to be a function of the relative doses of nicotinamide and streptozotocin and of the interval between injections.