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Effects of Sesamin and Curcumin on .DELTA.5-Desaturation and Chain Elongation of Polyunsaturated Fatty Acid Metabolism in Primary Cultured Rat Hepatocytes.
Abstract
Effects of sesamin and curcumin on delta 5-desaturation and chain elongation of polyunsaturated fatty acid (PUFA) were studied in rat primary cultured hepatocytes. When sesamin was added to culture medium containing 20:4 (n-3), rat hepatocytes after 24 h of incubation produced 20:5 (n-3) from 20:4 (n-3), whereas when incubated with 20:3 (n-6), the metabolite by delta 5-desaturation did not accumulate, and consequently, the ratio of 20:3 (n-6)/20:4 (n-6) increased with the amount of sesamin added. Curcumin was more effective than sesamin in this respect. Both sesamin and curcumin interfered with chain elongation of PUFAs. An addition of 18:3 (n-6) or 18:4 (n-3) increased the cellular concentrations of 20:3 (n-6) or 20:4 (n-3), respectively, but the simultaneous addition of sesamin or curcumin inhibited the chain elongation of C18 acids (the fatty acids with 18 carbons) into corresponding C20 and C18 acids. Similarly, the elongation from C20 of n-3 and n-6 families to C22 was also inhibited with sesamin and curcumin. These results suggested that: 1) sesamin and curcumin inhibited delta 5-desaturation of n-6 fatty acid, but not n-3 fatty acid in rat hepatocytes; 2) curcumin was more effective than sesamin; 3) chain elongation was also inhibited by sesamin and curcumin.
... However, the extent of this inhibition was much more pronounced with sesamin than with the other lignans (Shimizu et al., 1991). Similarly, in another in vitro study, Fujiyama-Fujiwara and colleagues examined the effects of sesamin and curcumin, a yellow pigment of turmeric used in curry powder, on Δ5 desaturation and chain elongation of n-3 and n-6 series of PUFAs in primary cultured male Wistar rat hepatocytes (Fujiyama-Fujiwara et al., 1992). Results indicated that the addition of 12.5 μg/ml of sesamin or 7.5 μg/ml of curcumin for 24 h resulted in the inhibition of Δ5 desaturation in the 20:3 (n-6) series, but not in the 20:4 (n-3) series of PUFAs, although these effects were more profound with curcumin than with sesamin (Fujiyama-Fujiwara et al., 1992). ...
... Similarly, in another in vitro study, Fujiyama-Fujiwara and colleagues examined the effects of sesamin and curcumin, a yellow pigment of turmeric used in curry powder, on Δ5 desaturation and chain elongation of n-3 and n-6 series of PUFAs in primary cultured male Wistar rat hepatocytes (Fujiyama-Fujiwara et al., 1992). Results indicated that the addition of 12.5 μg/ml of sesamin or 7.5 μg/ml of curcumin for 24 h resulted in the inhibition of Δ5 desaturation in the 20:3 (n-6) series, but not in the 20:4 (n-3) series of PUFAs, although these effects were more profound with curcumin than with sesamin (Fujiyama-Fujiwara et al., 1992). Further investigation also revealed the role that sesamin and curcumin play in the inhibition of chain elongation of PUFAs in both the n-3 and n-6 series, whereby the elongation of the 18:3 (n-6) and 18:4 (n-3) series into their corresponding 20:3 (n-6) and 20:4 (n-3) forms and to their subsequent C22 forms was prevented with the addition of sesamin and curcumin to the incubation medium (Fujiyama-Fujiwara et al., 1992). ...
... Results indicated that the addition of 12.5 μg/ml of sesamin or 7.5 μg/ml of curcumin for 24 h resulted in the inhibition of Δ5 desaturation in the 20:3 (n-6) series, but not in the 20:4 (n-3) series of PUFAs, although these effects were more profound with curcumin than with sesamin (Fujiyama-Fujiwara et al., 1992). Further investigation also revealed the role that sesamin and curcumin play in the inhibition of chain elongation of PUFAs in both the n-3 and n-6 series, whereby the elongation of the 18:3 (n-6) and 18:4 (n-3) series into their corresponding 20:3 (n-6) and 20:4 (n-3) forms and to their subsequent C22 forms was prevented with the addition of sesamin and curcumin to the incubation medium (Fujiyama-Fujiwara et al., 1992). ...
Sesamin is the major lignan constituent derived from Sesamum indicum seeds and sesame oil. Various studies have reported that sesamin possesses potent lipid-lowering properties. The lipid-lowering effects of sesamin have been mainly attributed to its ability in affecting key events in fatty acid and cholesterol metabolism and in lowering atherogenesis-triggering LDL, VLDL and TG levels, as well as in increasing atheroprotective HDL levels. In this review, we provide a comprehensive summary of the reported anti-hyperlipidemic effects of sesamin, presented both in vitro and in vivo. The molecular anti-hyperlipidemic properties of sesamin that underlie its well-documented anti-atherogenic effects are thoroughly discussed and analyzed. Studies focusing on the ability of sesamin to inhibit fatty acid synthesis, induce fatty acid oxidation, inhibit cholesterol synthesis and absorption and maintain macrophage cholesterol homeostasis are outlined. The effects of sesamin on circulating serum and liver lipid levels are also highlighted. Moreover, the anti-hyperlipidemic effects of sesamin are compared to those of other important sesame lignans like sesamolin and episesamin. Findings reveal that sesamin mainly exerts its anti-hyperlipidemic effects by targeting Δ5 desaturase, HMGCR, ABCA1 and ABCG1 through PPARα, PPARγ, LXRα, and SREBP signaling pathways. Overall, the amount of evidence supporting the anti-hyperlipidemic potential of sesamin in vitro and in vivo is compelling. A thorough understanding of the mechanisms underlying the anti-hyperlipidemic properties of sesamin is imperative for the possible employment of sesamin as an anti-hyperlipidemic and anti-atherogenic agent with minimal side effects.
... It is noteworthy that LA is oxidized to form oxidized LA metabolites (OXLAMs) that are the most abundant oxidized fatty acids in oxidized low density lipoprotein, which are potentially more atherogenic than unmodified low density lipoprotein. This implies that various factors that have a modulatory influence on LA metabolism such as antioxidants [9][10][11][12], phytochemicals [13][14][15][16][17][18], minerals [19], gender [20,21], age [22], and genetics [23] play a significant role in bringing about its (LA) beneficial action. Thus, there are many variables that modulate the metabolism of various fatty acids. ...
... In addition, some phytochemicals, particularly curcumin and sesamin, also downregulate Δ 5 . But, surprisingly, both curcumin and sesamin suppressed desaturation of w-6 fatty acids but not of w-3 fatty acids [16,73]. Curcumin is more effective than sesamin, while simultaneous use of both curcumin and sesamin had a greater suppressive effect on chain elongation, resulting in tissue accumulation of GLA and DGLA. ...
An imbalance of dietary lipids may potentially have a significant role in the pathobiology of some chronic diseases. Public health dietary fat recommendations have emphasized that low saturated fat, high monounsaturated fat, and high polyunsaturated fat with a lower ω-6 to ω-3 fatty acid ratio intake are necessary for normal health. However, such universal recommendations are likely to be hazardous, since the outcome of recommended lipid intake may depend on the consumption of other important dietary constituents that have an important role in the metabolism of lipids. In addition, consumption of fatty acids as per the individually tailored specific requirements in the context of other nutritional factors may have the potential to stabilize hormones, mood and sleep, and minimize adverse events. In support of this proposal, we review various factors that influence fatty acid metabolism, which need to be taken into consideration for appropriate utilization and consequently prevention of various diseases.
... It is noteworthy that LA is oxidized to form oxidized LA metabolites (OXLAMs) that are the most abundant oxidized fatty acids in oxidized low density lipoprotein, which are potentially more atherogenic than unmodified low density lipoprotein. This implies that various factors that have a modulatory influence on LA metabolism such as antioxidants [9][10][11][12], phytochemicals [13][14][15][16][17][18], minerals [19], gender [20,21], age [22], and genetics [23] play a significant role in bringing about its (LA) beneficial action. Thus, there are many variables that modulate the metabolism of various fatty acids. ...
... In addition, some phytochemicals, particularly curcumin and sesamin, also downregulate Δ 5 . But, surprisingly, both curcumin and sesamin suppressed desaturation of w-6 fatty acids but not of w-3 fatty acids [16,73]. Curcumin is more effective than sesamin, while simultaneous use of both curcumin and sesamin had a greater suppressive effect on chain elongation, resulting in tissue accumulation of GLA and DGLA. ...
Inflammation is the complex biological response of vascular tissue to harmful stimuli such as pathogens, damaged cells or irritants [1] that consists of both vascular and cellular responses. Inflammation is a protective attempt by the organism to remove the injurious stimuli and initiate healing process and to restore both structure and function. It should be understood that infection and inflammation are not synonymous: infection is caused by an exogenous pathogen while inflammation is the response of the organism to the pathogen. Inflammation may be local or systemic, and it can be acute or chronic. During the inflammatory process, the reaction of blood vessels is unique that leads to the accumulation of fluid and leukocytes in extravascular tissues. The reaction of blood vessels can be in the form of vasodilatation that is seen in the form of hyperemia at the site(s) of injury, that increases blood supply to the injured tissue/organ so that cellular elements, antibodies and nutrients can reach the site of injury in adequate amounts to eliminate the inflammation-inducing agent and/or repair process can be initiated once inflammation subsides. Thus, both injury and repair are two sides of the inflammatory process that are very closely intertwined such that it is difficult to separate these two processes. In fact, in majority of the instances, both inflammation to injury and repair occur almost simultaneously.
... This may be related to the capability of CUR to reduce the free fatty acids (FFA) by elevation of beta-oxidation activity [36]. This decreased endogenous polyunsaturated fatty acid synthesis [37] and inhibited TNF-α [38]. ...
Diabetes is associated with an increase in the production of free radicals, reduction of tetrahydrobiopterin (BH4, THB) levels and reduced bioavailability of nitric oxide (NO) in the vascular walls. In this contribution, we probed the effective role of curcumin nanoparticles (CUR-NPs) that prepared via solvent evaporation nanoprecipitation technique as potential system to attenuate endothelial dysfunction. In this technique, Tween 60 (polysorbate) was used as stabilizing agent for the prepared CUR-NPs and protect such nanoparticles from further agglomeration. BH4 levels and other parameters were estimated in diabetic rats. To this end, we dedicated 48 male albino rats, categorized into six groups; control (healthy rats), diabetic rats, along with four treated groups via oral administration of 0.2 mL/kg body weight/day of solutions of Tween 60 (60 mg/mL), free CUR (60 mg/mL), CUR-NPs1 (30 mg/mL), and CUR-NPs2 (60 mg/mL) for 30 days. Results showed that the mean level of malondialdehyde (MDA) has been significantly increased in diabetic group associated with a reduction of total antioxidant capacity, NO, and BH4 compared to control. These parameters were restored by the delivery of CUR-NPs-both doses in rats, compared with the two control groups that treated with Tween 60 and free CUR.
... Results demonstrated that curcumin inhibits the Δ5 desaturation of n-6 series FAs (increases the 20:3n-6 to 20:4n-6 ratio), but not Δ5 desaturation of n-3 series FAs (decreases the 20:4n-3 to 20:5n-3 ratio). The authors suggested that Δ5 desaturase acts differently in metabolism and affinity to both types of PUFAs (n-6 and n-3; Fujiyama-Fujiwara et al., 1992). Moreover, the effects of curcumin on Δ5 and Δ6 desaturase activity, which was measured by DGLA to ARA ratio, were studied in vitro and in vivo systems. ...
Free fatty acids (FFAs) and fatty acid synthesis (FAS) activity have significantly contributed to disease states such as insulin resistance, obesity, type 2 diabetes, myocardial infarction, blood pressure, and several types of cancer. Currently, several treatment options are available for patients with these conditions. Due to safety concerns, adverse effects, limited efficacy, and low tolerability associated with many medications, the identification of novel agents with less toxicity and a more favorable outcome is warranted. Curcumin is a phenolic compound derived from the turmeric plant with various biological activities, including anticarcinogenic, antioxidant, antiinflammatory, and hypolipidemic properties. PubMed, Scopus, and Web of Science were searched up to February 2020 for studies that demonstrated the efficacy and mechanisms of curcumin action on FFAs, FAS, and β‐oxidation activity, as well as the desaturation system. Most of the evidence is in‐vivo and in‐vitro studies that demonstrate that curcumin possesses regulatory properties on FFAs levels through its effects on FAS and β‐oxidation activity as well as desaturation system, which could improve insulin resistance, obesity, and other FFAs‐related disorders. The present study provides a review of the existing in‐vitro, in‐vivo, and clinical evidence on the effect of curcumin on FFAs and FAS activity, β‐oxidation, and desaturation system.
... This may be related to the capability of CUR to reduce the free fatty acids (FFA) by elevation of beta-oxidation activity [36]. This decreased endogenous polyunsaturated fatty acid synthesis [37] and inhibited TNF-α [38]. ...
Diabetes is associated with an increase in the production of free radicals, reduction of tetrahydrobiopterin (BH4, THB) levels and reduced bioavailability of nitric oxide (NO) in the vascular walls. In this contribution, we probed explored the effective efficient role of curcumin nanoparticles (CUR-NPs) that prepared via solvent evaporation nanoprecipitation technique as potential system to attenuate endothelial dysfunction. In this technique, Tween 60 (polysorbate) was used as stabilizing agent for the prepared CUR-NPs and protect such nanoparticles from further agglomeration. BH4 levels and other parameters were estimated in diabetic rats. To this end, we dedicated 48 male albino rats, categorized into six groups; control (healthy rats), diabetic rats, along with four treated groups via oral administration of 0.2 mL/kg body weight/day of solutions of Tween 60 (60 mg/mL), free CUR (60 mg/mL), CUR-NPs1 (30 mg/mL), and CUR-NPs2 (60 mg/mL) for 30 days. Results showed that the mean level of malondialdehyde (MDA) has been significantly increased in diabetic group associated with a reduction of total antioxidant capacity, NO, and BH4 compared to control. These parameters were restored by the delivery of CUR-NPs – both doses in rats, compared with the two control groups that treated with Tween 60 and free CUR
... Rose oil and rose water have many therapeutic effects. [19] Hair care: ...
Objective: Numerous herbal plants are available naturally; they having different chemical constituents used in cosmetics preparations. This review is based on focusing on the cosmeceuticals intended to enhance the health and beauty of skin. Methods: The isolated compounds from the herbal plants like coconut oil, sunflower oil, ojoba oil, olive oil, aloe-vera, were studied their skin care effects and adverse reaction. The herbs like rhodiolarosea, carrot, gingko, and turmeric were studied for their anti-aging property. Herbal plants like henna, neem were studied their antidandruff treatment. Herbal likes green tea, calendula, turmeric, shitake, rose oil were evaluated their skin protection capacity. Amla, eucalyptus oil were tested their hair growth character and also studied the antioxidant property of some vitamins. Results: The results obtained from the study, proved that effective and safe, when used as a moisturizer with absence of adverse reaction. Herbs are rich in vitamins, they have anti-aging, revitalizing and rejuvenating agent. Herbs produce anti-fungal, anti-bacterial and pain relieving that can treat dandruff. The plants produce antiseptic , anti-inflammatory, anti-oxidant, and insect repellent, help in wound healing and skin protection. Herbs have vitamins and other constituents. They provide nutrition to hair and also cause darkening of hair. It also provides antioxidant and photo aging on the skin. Conclusions: The current review highlights importance of herbal cosmetics, the herbs used in them and their advantages over the synthetic counterparts. The present study revealed that herbal cosmetics are very safe and does not produce any toxic and adverse reactions compare to marketed cosmetics products. We suggest that, use herbal cosmetics in future, will avoid skin problems.
... Curcumin is shown to influence PUFA levels by interfering with Δ desaturase enzyme which may affect essential fatty acid levels [24,25]. Rats were given curcumin in native or nanoemulsion form with SNO or LSO daily for a period of 60 days as described in methods. ...
Docosahexaenoic acid (DHA) is an important long chain omega-3 polyunsaturated fatty acid (PUFA) primarily found in marine fishes. The diets of vegetarian population do not contain preformed DHA, but they can derive it from shorter chain α-linolenic acid (ALA) found in plant oils. However, the conversion efficiency of ALA to DHA is minimal in human adults. This may cause insufficiency of DHA in the vegetarian population. Curcumin, diferuloyl methane found in the spice turmeric, has the potential to increase the formation of DHA from ALA by activating the enzymes FADS2 and elongase 2. The present study was designed to prepare curcumin nanoemulsion using phospholipid core material (LipoidTM) and exploring the possibility of enhancing its bioavailability and its impact on DHA levels in rats. Curcumin was dissolved in coconut oil (CNO, MCFA rich), Sunflower oil (SNO, n-6 PUFA rich) or Linseed oil (LSO, n-3 PUFA rich) and nanoemulsions were prepared after mixing with LipoidTM using high pressure homogenizer. The nanoemulsions were fed to weaning rats for 60 days along with AIN-93 diets. Rats fed nanoemulsion containing curcumin in LSO showed high levels of curcumin in serum liver, heart and brain. Significant increase in DHA levels of serum and tissue lipids were observed in rats given LSO with curcumin in nanoemulsions. Therefore, supplementation of diets with ALA rich LSO and curcumin could increase DHA concentrations in serum, liver, heart and brain lipids which have implications for meeting the DHA requirements of vegetarian populations.
... Secondly, curcumin suppresses tumor invasion by down-regulation of matrix metalloproteinases and cell surface adhesion molecules (Lin et al., 1998;Fenton et al., 2002;Lee et al., 2006). Thirdly, curcumin inhibits angiogenic cytokines leading to suppression of angiogenesis (Shin et al., 2001;Leyon and Kuttan, 2003;Bobrovnikova-Marjon et al., 2004) and lastly the antiinflammatory and cytotoxic effects of curcumin contribute to its antitumor activity (Srivastava, 1989;Fujiyama-Fujiwara et al., 1992;Ammon et al., 1993). ...
Curcuma longa has long been used in China and India as anti-inflammatory agent to treat a wide variety of conditions and also as a spice for varied curry preparations. The chemoprofile of the Curcuma species exhibits the presence of varied phytochemicals with curcumin being present in all three species but AA only being shown in C. longa. This study explored the effect of a curcumin/AA combination on human cancer cell lines. The curcumin/AA combination was assessed by isobologram analysis using the Loewe additivity drug interaction model. The drug combination showed additive cytotoxicity toward CCRF-CEM and CEM/ADR5000 leukemia cell lines and HCT116p53+/+ and HCT116p53−/− colon cancer cell line, while the glioblastoma cell lines U87MG and U87MG.ΔEGFR showed additive to supra-additive cytotoxicity. Gene expression profiles predicting sensitivity and resistance of tumor cells to induction by curcumin and AA were determined by microarray-based mRNA expressions, COMPARE, and hierarchical cluster analyses. Numerous genes involved in transcription (TFAM, TCERG1, RGS13, C11orf31), apoptosis-regulation (CRADD, CDK7, CDK19, CD81, TOM1) signal transduction (NR1D2, HMGN1, ABCA1, DE4ND4B, TRIM27) DNA repair (TOPBP1, RPA2), mRNA metabolism (RBBP4, HNRNPR, SRSF4, NR2F2, PDK1, TGM2), and transporter genes (ABCA1) correlated with cellular responsiveness to curcumin and ascorbic acid. In conclusion, this study shows the effect of the curcumin/AA combination and identifies several candidate genes that may regulate the response of varied cancer cells to curcumin and AA.
... Curcumin is the phytochemical that gives a yellow color to turmeric and is now recognized as being responsible for most of the therapeutic effects [42]. Uses of turmeric include antiseptic, analgesic, anti-inflammatory, antioxidant, antimalarial, insect-repellant, and other activities associated to turmeric [43][44][45][46] ( Figure 13). ...
Herbal cosmetics are formulated, using different cosmetic ingredients to form the base in which one or more herbal ingredients are used to cure various skin ailments. The name itself suggests that herbal cosmetics are natural and free from all the harmful synthetic chemicals which otherwise may prove to be toxic to the skin. Compared to other beauty products, natural cosmetics are safe to use. Cosmeceuticals are cosmetic-pharmaceutical hybrid products intended to improve the health and beauty of the skin by providing a specific result, ranging from acne-control and anti-wrinkle effects, to sun protection. Cosmeceuticals have medicinal benefits which affect the biological functioning of skin depending upon type of functional ingredients they contain. These are cosmetic products that are not just used for beautification but for different skin ailments. These products improve the functioning/texture of the skin by boosting collagen growth by eradicating harmful effects of free radicals, maintains keratin structure in good condition and making the skin healthier. There are numerous herbs available naturally having different uses in cosmetic preparations for skincare, hair care and as antioxidants. The current review highlights importance of herbal cosmetics, the herbs used in them and their advantages over the synthetic counterparts.
... Sesame lignans are known to inhibit the course of fatty acid metabolism, in vivo in animal models, and also in microorganisms by specifically inhibiting the rate limiting enzyme Δ5 desaturase (Fujiyama-Fujiwara et al. 1992). In the present study, all the 3 lignans show inhibition of lipid peroxidation, in vitro, resulting in prevention of β-carotene bleaching and also formation of linoleate peroxyl radical. ...
Antioxidants protect the body from various disease conditions through their ability to neutralize the effects of free radicals. Synthetic antioxidants are extensively used in processed foods for prevention of oxidation and retention of sensory quality. Consumer awareness and preference has led to a vigorous interest in the search for natural antioxidants. Sesamin and sesamolin, the major lignans present in sesame oil, are known for their antioxidative properties. Roasted sesame oil has a higher concentration of sesamol, the thermally degraded product of sesamolin, which is considered a more potent antioxidant compared to its parent molecule. The isolated lignans and sesamol were tested for their antioxidant, free radical scavenging and antibacterial properties. Sesamol is the best antioxidant and free radical scavenger amongst the molecules studied with IC50 value of 5.44 μg / mL (DPPH radical scavenging activity). Antibacterial assays against food borne pathogens revealed sesamol to be an antimicrobial agent with minimal inhibitory concentration (MIC) of 2 mg /mL in the culture. Its activity was synergistic with γ-tocopherol, also present in sesame seeds. Inhibition of browning (60-65 %) in fruit pulps (apple, banana and potato) was observed in presence of 20 μM sesamol.
... Our findings also concurred with the results from another salmonid in vitro trial when ALA incubation with sesamin increased DHA levels in hepatocytes (Trattner, Ruyter et al., 2008). Incubating rat hepatocytes with ETA in the presence of sesamin produced significantly greater concentrations of EPA, whereas dihomo-c-linolenic acid (DGLA) in the same media did not increase the content of ARA (Fujiyama-Fujiwara, Umeda, & Igarashi, 1992;Shimizu, Akimoto, Shinmen, Kawashima, Sugano, & Yamada, 1991). Several other studies demonstrated the preferential effect of sesamin in inhibiting the FAD5 enzyme activity in pathways of LC-PUFA biosynthesis and metabolite production in vertebrates (Akimoto et al., 1993;Chavali et al., 1998;Yanes et al., 2010); LC-PUFA were esterified into TAG and FA b-oxidation increased (Umeda-Sawada, Ogawa, Nakamura, & Igarashi, 2001). ...
Sesamin, a major sesame seed lignan, has diverse biological functions including the modulation of molecular actions in lipid metabolic pathways and reducing cholesterol levels. Vertebrates have different capacities to biosynthesize long-chain PUFA from dietary precursors and sesamin can enhance the biosynthesis of ALA to EPA and DHA in marine teleost. Early juvenile barramundi, Lates calcarifer, were fed for two weeks on diets rich in ALA or SDA derived from linseed or Echium plantagineum, respectively. Both diets contained phytosterols and less cholesterol compared with a standard fish oil-based diet. The growth rates were reduced in the animals receiving sesamin regardless of the dietary oil. However, the relative levels of n-3 LC-PUFA in total lipid, but not the phospholipid, increased in the whole body by up to 25% in animals fed on sesamin with ALA or SDA. Sesamin reduced the relative levels of triacylglycerols and increased polar lipid, and did not affect the relative composition of phospholipid subclasses or sterols. Sesamin is a potent modulator for LC-PUFA biosynthesis in animals, but probably will have more effective impact at advanced ages. By modulating certain lipid metabolic pathways, sesamin has probably disrupted the body growth and development of organs and tissues in early juvenile barramundi.
Lipid intake, and its appropriate quantity and quality, are important for the prevention of lifestyle-related diseases caused by obesity. The authors investigated the action of polyunsaturated fatty acids in regulating biological functions and their effects on body metabolism. Since the biological effects of consuming different vegetable oils cannot be explained by fatty acid composition alone, we have also studied the trace constituents of fats and oils. Here, we outline the results of our research on vitamin E. We have shown that tocotrienols, which are abundant in palm oil, maintain insulin secretion during a high-fat diet. Our findings also suggest that tocotrienols may inhibit fibrosis in the early stages of non-alcoholic steatohepatitis (NASH). In addition, the risk of osteoporosis associated with high vitamin E intake was examined from a nutritional perspective under various conditions. These series of studies suggest the need to consider not only fatty acid composition but also the influence of trace constituents of food when offering nutritional guidance on appropriate lipid intake.
Herbal cosmetics are formulated by using different cosmetic ingredients to form the base in which one or more herbal ingredients are wont to cure various skin ailment. The name suggests that herbal cosmetics are natural and free from all the harmful synthetic chemicals which otherwise may convince be toxic to the skin. Compared to other beauty products, natural cosmetics are safe to use. They are hypo-allergenic and tested and proven by dermatologists to be safe to use anytime, anywhere. Cosmeceuticals are cosmeticpharmaceutical hybrid products intended to enhance the health and wonder of the skin by providing a selected result, starting from acne-control and anti-wrinkle effects to sun protection. Cosmeceuticals have medicinal benefits which affect the biological functioning of skin depending upon the sort of functional ingredients they contain. These are cosmetic products that aren't just used for beautification but for different skin ailments. These products improve the functioning/texture of the skin by boosting collagen growth by eradicating harmful effects of free radicals, maintain keratin structure in good condition, and making the skin healthier. There are numerous herbs available naturally having different uses in cosmetic preparations for skin care, hair care, and as antioxidants. The current review highlights the importance of herbal cosmetics, the herbs used in them, and their advantages over their synthetic counterparts.
Knocking down delta-5-desaturase (D5D) by siRNA or shRNA is a promising strategy to achieve 8-hydroxyoctanoic acid (8-HOA) production for cancer inhibition. However, the RNAi-based strategy to stimulate 8-HOA is restricted due to endonucleases mediated physiological degradation and off-target effects. Thus, to get persistent 8-HOA in the cancer cell, we recognized a D5D inhibitor Iminodibenzyl. Here, we have postulated that Iminodibenzyl, by inhibiting D5D activity, could shift the di-homo-gamma-linolenic acid (DGLA) peroxidation from arachidonic acid to 8-HOA in high COX-2 microenvironment of 4T1 and MDA-MB-231 breast cancer cells. We observed that Iminodibenzyl stimulated 8-HOA caused HDAC activity reduction resulting in intrinsic apoptosis pathway activation. Additionally, reduced filopodia and lamellipodia, and epithelial-mesenchymal transition markers give rise to decreased cancer cell migration. In the orthotopic breast cancer model, the combination of Iminodibenzyl and DGLA reduced tumor size. From in vitro and in vivo studies, we concluded that Iminodibenzyl could reprogram COX-2 induced DGLA peroxidation to produce anti-cancer activity.
Sesame seed has higher oil content (around 50%) than most of the known oilseeds, although because of the labor‐intensive harvesting of the seeds, its production is far less than the major oilseeds such as soybean or rapeseed. Sesame oil is generally regarded as a high‐priced and high‐quality oil. It is one of the most stable edible oils despite its high degree of unsaturation. The presence of natural phytochemicals accounts for both the superior stability of sesame oil and the beneficial physiological effects of sesame.
Marine tropical carnivorous (MTC) fish are less tolerant to high dietary lipid compared with cold and temperate climate fish. However, insufficient n-3 long-chain (≥C 20) polyunsaturated fatty acids (LC-PUFA) compromises MTC fish health and growth which requires attention when choosing lipid sources in aqua-feed formulations. Fish oil (FO) has been the major lipid source for feeding key MTC fish. We estimated that more than 200 thousand tonnes of FO were used to feed farmed MTC fish in 2016, representing nearly 25% of global FO production. Nevertheless, recent increases in FO prices and demand, and the foreseen inability of wild fisheries to produce sufficient FO in the future, have created a need for cheaper and more sustainable alternatives. Meta-analysis showed that feeding vegetable oils (VO) to MTC fish can slightly reduce their growth, with a marked decrease in n-3 LC-PUFA content in the fish tissues corresponding with the increased replacement of FO and fishmeal in the diet. Rendered terrestrial animal fat or modulating the bioconversion of n-3 LC-PUFA precursors in VO can be utilised further in MTC fish nutrition with more research recommended on these approaches. Oils and oil-rich meals from non-food marine organisms are rich in n-3 LC-PUFA and represent an underutilised alternative to FO for tropical aquaculture. With oils rich in n-3 LC-PUFA produced from transgenic plants presently gaining regulatory approvals and becoming available as a renewable alternative to FO, aquaculture in the tropics and around the globe is ready to leap into a new phase of sustainable expansion.
Sesame seed and its oil have been utilized as important foodstuffs for about 6000 years. A cultivated sesame species, Sesamum indicum L., is believed to have originated in the Savanna of central Africa spreading to Egypt, India, the Middle East, China, and elsewhere. Sesame seed and oil have been evaluated as representative health foods and widely used for their good fl avor and taste (Namiki and Kobayashi, 1989). Historically, an old text, the Thebes Medicinal Papyrus (1552 bc), found in Egypt, describes the medicinal effect of sesame seed as a source of energy. Hippocrates in Greece noted its high nutritive value. A Chinese book (300 bc), which explains medicinal effects of various plants, describes sesame as a good food having various physiological effects, especially useful for providing energy, a tranquil frame of mind, and retarding the process of aging when eaten over a long period. Further, in traditional Indian medicine, Ayurveda, sesame oil has been used as the basal oil for human body massage since 700-1100 bc (Weiss, 1983; Joshi, 1961). The magic words, “Open, sesame!" from the Arabian Night stories are very familiar throughout the world and may have originated from the abrupt opening of the sesame capsule to scatter seeds and also to show sesame’s magic power. In Japan people have traditionally believed that sesame is very good for health (Namiki, 1990, 1995). Despite such high values placed on sesame seed and oil, there have been few scientifi c studies to elucidate their functions. Initiated from the studies on the protective effects of food components against the lethal effects of radiation (Sumiki et al., 1958), many antioxidants and antimutagens in various foods have extensively studied by author’s group (Kada, 1978; Namiki, 1990; Osawa, 1997). Among them, studies on the traditionally believed health functions of sesame have been especially noted, and various interesting functions such as the antioxidation and antiaging effects with tocopherols, serum lipid-lowering effect, blood pressure-lowering effect, and other functions have been elucidated (Namiki, 1998, 2007).
This study was carried out to test the growth inhibitory effects of sesamolin obtained from sesame seeds. Sesamolin inhibited the growth of human leukemia HL-60 cells in cultures and the synthesis of macromolecules in dose- and time-dependent manners. Sesamolin in the 60-100 μg/ml range was cytostatic. At concentrations greater than 200 μg/ml sesamolin was cytocidal to HL-60 cells and at 60 μg/ml inhibited the synthesis of DNA, RNA and protein in HL-60 cells by 35.1, 6.1, and 5.3%, whereas at 200 μg/ml these inhibitions were 86.8, 81.5 and 96.7%, respectively. The inhibitory effect of sesamolin on DNA synthesis was irreversible.
Some historical facts on and botanical descriptions of sesame are given. Some flavor studies of raw and roasted sesame seeds and oils are described. Composition and some usages are also briefly reported. Sesame has long been regarded in the Orient as a health food which increases energy and prevents aging. Sesame oil has been known empirically as a cooking oil which is highly resistant to oxidative deterioration in comparison with other edible oils. Until recently there were no scientific studies to elucidate these interesting aspects of sesame seed and oil, but the author and members of his group initiated studies on the chemical elucidation of antioxidative principles of sesame seed and oil, and extensively investigated the antiaging effect of sesame. Presence of various new antioxidative lignan phenol compounds in sesame seed and oil is described. Sesaminol has been identified as a new antioxidative principle in raw sesame salad oil. The mechanism of the superior antioxidative activity of roasted sesame oil is being elucidated and is consistent with the synergistic effect of the browning products with tocopherol, sesamol, and sesamin. Noticeable results concerning the antiaging effect of sesame have been shown in a series of animal experiments. The suppressive effect on senescence in mice by long‐term feeding of sesame was demonstrated. Sesame lignans had a synergistic effect on vitamin E activities when added to tocopherols. The addition of sesame lignans, especially that of antioxidative lignan sesaminol in the diets of rats, markedly enhanced vitamin E activity of γ‐tocopherol to the same level of α‐tocopherol, and also significantly enhanced the vitamin E activity of α‐tocopherol. These effects were accompanied by a marked increase in the concentrations of these tocopherols in blood and liver. The enhancement of vitamin E activity by lignans is very important from the viewpoint of evaluating vitamin E activity as well as the antiaging effect of various foods. Various interesting physiological activities of sesame lignans in animal and human tests were shown, such as hypocholesterolemic activity, suppressive activity of chemically induced cancer, and enhancing effect on various liver activities involving detoxification of carbon tetrachloride and ethanol. These recent developments in chemical and physiological studies on sesame seed and oil seem to partially unveil the mystery surrounding sesame though there remain many interesting physiological activities in various aspects of advanced nutritional and phsyiological sciences which need to be clarified. These recent studies demonstrate that sesame, though a minor constituent of daily diets, plays an important role in developing the potential powers of other food constituents as well as markedly raising food quality, not just in the aroma and taste, but also in nutritional and physiological aspects. Because much attention has been focused on the effect of the daily diet on health, especially on circulatory disorders, carcinogenesis, and senility, it seems that sesame seed and oil should be considered as one of the more valuable foods for good health and for good quality of life in general.
The structure-activity relationship of allergy enhancing and suppressing factors in foodstuffs was summarized in this text. Polyunsaturated fatty acids (PUFA) enhance allergic response by enhancing IgE production and by suppressing production of other antibodies in rat lymphocytes. Because the expression of IgE production enhancing activity was inhibited by lipophilic antioxidants, lipid oxidation reaction seems to have participated in the activity. Xanthene dyes, a group of synthetic dyes, also exert IgE production enhancing effect, and the activity is dependent on the degree of halogenation. On the other hand, PUFA exert anti-allergic effect by suppressing the release of chemical mediators from rat peritoneal exudate cells, and the activity becomes stronger with the increase in the number of double bonds. In addition, antioxidants such as tea polyphenols (TP) and flavonoids exert anti-allergic effect mainly due to the suppression of chemical mediator release. Histamine release suppressing activity is observed in triphenol derivatives, but not in diphenols. On the contrary, LTB4 release suppressing activity is observed in mono and diphenolic derivatives with antioxidative activity. These results suggest that various food components have immunoregulatory activity and that optimization of their intake is desirable.
Background and aim:
Curcumin, an active component derived from dietary spice turmeric (Curcuma longa), has been demonstrated antihyperglycemic, antiinflammatory and hypocholesterolemic activities in obesity and diabetes. These effects are associated with decreased level of circulating free fatty acids (FFA), however the mechanism has not yet been elucidated. The flux of FFA and glycerol from adipose tissue to the blood stream primarily depends on the lipolysis of triacylglycerols in the adipocytes. Adipocyte lipolysis is physiologically stimulated by catecholamine hormones. Tumor necrosis factor-α (TNFα) stimulates chronic lipolysis in obesity and type 2 diabetes. In this study, we examined the role of curcumin in inhibiting lipolytic action upon various stimulations in 3T3-L1 adipocytes.
Methods:
Glycerol release from TNFα or isoproterenol-stimulated 3T3-L1 adipocytes in the absence or presence of curcumin was determined using a colorimetric assay (GPO-Trinder). Western blotting was used to investigate the TNFα-induced phosphorylation of MAPK and perilipin expression. Fatcake and cytosolic fractions were prepared to examine the isoproterenol-stimulated hormone-sensitive lipase translocation.
Results:
Treatment with curcumin attenuated TNFα-mediated lipolysis by suppressing phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2) and reversing the downregulation of perilipin protein in TNFα-stimulated adipocytes (p<0.05). The acute lipolytic response to adrenergic stimulation of isoproterenol was also restricted by curcumin (10-20 μM, p<0.05), which was compatible with reduced perilipin phosphorylation(29%, p<0.05) and hormone-sensitive lipase translocation(20%, p<0.05).
Conclusions:
This study provides evidence that curcumin acts on adipocytes to suppress the lipolysis response to TNFα and catecholamines. The antilipolytic effect could be a cellular basis for curcumin decreasing plasma FFA levels and improving insulin sensitivity.
Sesame seed has higher oil content (around 50%) than most of the known oilseeds although its production is far less than the major oilseeds such as soybean or rapeseed due to labor-intensive harvesting of the seeds. Sesame oil is generally regarded as a high-priced and high-quality oil. It is one of the most stable edible oil despite its high degree of unsaturation. The presence of lignan type of natural antioxidants accounts for both the superior stability of sesame oil and the beneficial physiological effects of sesame.
Water-soluble (cacao pigment, cochineal pigment, corn pigment, betanin, carthamus yellow, and monascus pigment) and water-insoluble (gardenia yellow, laccaic acid, bixin, and curcumin) natural colorings inhibited IgE production by rat spleen lymphocytes at 10 and microM, respectively. Although many of these colorings only inhibited the production of IgG and IgM at high concentrations, the water-insoluble colorings enhanced IgM production even at 1 microM. These results suggest that natural colorings have immunoglobulin production-regulating activity.
Changes in the hepatic concentration of n-3 fatty acids, e.g., eicosapentaenoic acid and linolenic acid, were significantly reduced by their simultaneous administration with sesamin, whereas there was no such effect of sesamin for n-6 and n-9 fatty acids. However, there was no significant difference in lymphatic absorption between eicosapentaenoic acid (n-3) and arachidonic acid (n-6), irrespective of the presence of absence of sesamin.
The effect of retinol deficiency and curcumin/turmeric on lipid peroxidation and fatty acid profile was studied in liver, kidney, spleen and brain microsomes of rats. Results revealed an increase in lipid peroxidation in retinol deficient liver by 32%, kidney 30%, spleen 24% and brain 43% compared to the controls. Feeding 0.1% curcumin or turmeric for three weeks in diet to retinol deficient rats reduced the lipid peroxidation respectively to 12.5 or 22.6%, in liver, 23.7 or 24.1% in kidney, 14.4 or 18.0% in spleen and 16.0 or 31.4% in brain. Retinol deficiency lead to a reduction in the essential fatty acids. In liver C18:1 showed a reduction by 45.6%, C18:2 by 31.6% and C20:4 by 22.8%. In kidney C18:1 was reduced by 33.6%, 18:2 by 24.6% and 20:4 by 13.7%. In spleen and brain C18:1 showed a reduction by 10.2% and 33.9%, C18:2 by 37.9% and 12.1% and C20:4 by 15.7% and 35.3% respectively. Curcumin and turmeric fed group showed a significant increase in the abnormally reduced fatty acid levels.
The anti-inflammatory properties of essential fatty acid deficiency or n-3 polyunsaturated fatty acid supplementation have been attributed to a reduced content of arachidonic acid (AA; 20:4 n-6). An alternative, logical approach to depleting AA would be to decrease endogenous synthesis of AA by selectively inhibiting the delta5 and/or the delta6 fatty acid desaturase. High-throughput radioassays were developed for quantifying delta5, delta6, and delta9 desaturase activities in vitro and in vivo. CP-24879 (p-isopentoxyaniline), an aniline derivative, was identified as a mixed delta5/delta6 desaturase inhibitor during the screening of chemical and natural product libraries. In mouse mastocytoma ABMC-7 cells cultured chronically with CP-24879, there was a concentration-dependent inhibition of desaturase activity that correlated with the degree of depletion of AA and decreased production of leukotriene C4 (LTC4). Production of LTC4 was restored by stimulating the cells in the presence of exogenous AA, indicating that endogenous AA was limiting as substrate. In the livers of mice treated chronically with the maximally tolerated dose of CP-24879 (3 mg/kg, t.i.d.), combined delta5/delta6 desaturase activities were inhibited approximately 80% and AA was depleted nearly 50%. These results suggest that delta5 and/or delta6 desaturase inhibitors have the potential to manifest an anti-inflammatory response by decreasing the level of AA and the ensuing production of eicosanoids.
In this study, we examined the effect of dietary arachidonic acid (AA) and sesame lignans on the content and n-6/n-3 ratio of polyunsaturated fatty acid (PUFA) in rat liver and the concentrations of triglyceride (TG) and ketone bodies in serum. For 4 wk, rats were fed two types of dietary oils: (i) the control oil diet groups (CO and COS): soybean oil/perilla oil = 5:1, and (ii) the AA-rich oil group (AO and AOS): AA ethyl esters/palm oil/perilla oil = 2:2:1, with (COS and AOS) or without (CO and AO) 0.5% (w/w) of sesame lignans. Dietary AA and sesame lignans significantly affected hepatic PUFA metabolism. AA content and n-6/n-3 ratio in the liver were significantly increased in the AO group, despite the dietary total of n-6 PUFA being the same in all groups, while AOS diet reduced AA content and n-6/n-3 ratio to a level similar to the CO and COS groups. These results suggest that (i) dietary AA considerably affects the hepatic profile and n-6/n-3 ratio of PUFA, and (ii) dietary sesame lignans reduce AA content and n-6/n-3 ratio in the liver. In the AO group, the concentration of acetoacetate was significantly increased, but the ratio of beta-hydroxybutyrate/acetoacetate was decreased. On the other hand, the AO diet increased the concentration of TG in serum by almost twofold as compared to other groups. However, the AOS diet significantly reduced serum TG level as compared to the AO group. In addition, the AOS diet significantly increased the acetoacetate level, but reduced the beta-hydroxybutyrate/acetoacetate ratio. These results suggest that dietary sesame lignans promote ketogenesis and reduce PUFA esterification into TG. This study resulted in two findings: (i) sesame lignans inhibited extreme changes of the n-6/n-3 ratio by reducing hepatic PUFA content, and (ii) the reduction of hepatic PUFA content may have occurred because of the effects of sesame lignans on PUFA degradation (oxidation) and esterification.
We examined the effect of three dietary fats, safflower oil (SAF) rich in linoleic acid, borage oil (BOR) rich in gamma-linolenic acid, and perilla oil (PER) rich in alpha-linolenic acid, on the lipid metabolism, and chemical mediator and immunoglobulin levels in Sprague-Dawley rats, as well as the dietary effect of sesame-derived antioxidative sesamin. The serum cholesterol, phospholipid, triglyceride, prostaglandin E2 level and splenic leukotriene B4 level were lower in the rats fed on BOR or PER than in those fed on SAF. SES feeding suppressed the expression of the lipid-decreasing effect of BOR, but not in the rats fed on PER. In respect of the fatty acid composition of the liver and spleen, PER feeding gave a lower arachidonic acid level, and higher eicosapentaenoic and docosahexaenoic acid levels than SAF feeding did, while the effect of BOR feeding was marginal. The effect of SES feeding on fatty acid composition was much smaller than that of dietary fats. In respect of immunoglobulin production, PER + SES feeding gave the lowest IgE productivity in the mesenteric lymph node lymphocytes. These results suggest that PER feeding regulated lipid metabolism and exerted an anti-allergic effect by a different mechanism from that with BOR feeding.
In this study, we examined the distribution and metabolism of refined sesame oil lignans (sesamin and episesamin) in rat. For 8 wk rats were fed the diet including 0.5% (w/w) sesame lignans (sesamin and episesamin) with 5% (w/w) corn oil or eicosapentaenoic acid (EPA)-rich oil. The concentrations of sesamin and episesamin in rat liver after their administration for 8 wk were very low; both of them were less than 0.5 microgram/g liver. These were observed in both oil groups although the fatty acid compositions of dietary oils were completely different. No significant difference existed in lymphatic absorption between sesamin and episesamin. To investigate the distribution of sesamin and episesamin in rats, the concentrations of sesamin and episesamin were determined in tissues and serum within 24 h after administration to rats. Sesamin and episesamin may be, at first, incorporated into the liver and then transported to the other tissues (lung, heart, kidney, and brain). They are lost from the body within 24 h after administration. There was no significant difference in lymphatic absorption between sesamin and episesamin, but the amount of sesamin was significantly lower than that of episesamin in all tissues and serum. These results suggest that sesamin is absorbed in lymph the same as episesamin, but that sesamin is subsequently metabolized faster by the liver.
The effects of dietary sesamin on the hepatic metabolism of arachidonic (AA) and eicosapentaenoic (EPA) acids, were investigated with respect to their beta-oxidation and secretion as triacylglycerol (TG). For 2 wk, rats were fed three types of dietary oils: (i) corn oil (control) group; (ii) EPA group: EPA ethyl esters/rapeseed oil = 2:3; (iii) AA group: AA ethyl esters/palm oil/perilla oil = 2:2:1, with or without 0.5% (w/w) of sesamin. Dietary sesamin significantly increased the activities of hepatic mitochondrial and peroxisomal fatty acid oxidation enzymes (mitochondrial carnitine acyltransferase I, acyl-CoA dehydrogenase, and peroxisomal acyl-CoA oxidase). Dietary EPA increased mitochondrial carnitine acyltransferase I and peroxisomal acyl-CoA oxidase. Dietary AA, however, had an effect on peroxisomal acyl-CoA oxidase only. In whole liver and the TG fraction, EPA and AA concentrations were significantly increased by dietary EPA and AA, respectively, and were decreased by dietary sesamin. In hepatic mitochondria and peroxisomes, EPA concentration was increased by dietary EPA, but AA was not changed by dietary AA. The addition of dietary sesamin to the EPA-supplemented diet significantly decreased the EPA concentration compared to concentrations found with consumption of dietary EPA alone. These results suggest that sesamin increased beta-oxidation enzyme activities and reduced hepatic EPA and AA concentrations by degradation. The stimulating effect of sesamin on beta-oxidation, however, was more significant in the EPA group than in the AA group. Hepatic AA concentration was altered by the joint effect of sesamin through esterification into TG and the stimulation of beta-oxidation.
In this study, we examined the effects of sesamin and vegetable oil on the concentrations of polyunsaturated fatty acid (PUFA) and lipids (triacylglycerol, free cholesterol, and phospholipid), and beta-oxidation enzyme activities in the rat liver. Rats were fed a diet containing 5% (low-fat diet) or 20% (high-fat diet) salad oil (rapeseed oil: soybean oil, 7:3) with or without sesamin (0.5% w/w) for 4 wk. As a result, the concentrations of linoleic acid (LA, n-6), alpha-linolenic acid (ALA, n-3), and total PUFA in the liver increased significantly as the result of the high-fat diet. In the high-fat diet groups, sesamin administration decreased the concentrations of LA, ALA, and total PUFA to almost the same level as the low-fat diet group, while it increased the concentrations of dihomo-gamma-linolenic acid (DGLA, n-6) and arachidonic acid (AA, n-6). The activities of carnitine acyltransferase and acyl-CoA dehydrogenase in liver mitochondria were enhanced by the intake of the high-fat diet, and were further enhanced by the administration of sesamin. Peroxisomal acyl-CoA oxidase activity was also enhanced by sesamin, while it was not affected by the dietary fat level. These results suggest that sesamin suppressed the increase of hepatic PUFA concentration caused by feeding the high-fat diet through enhancing the enzyme activities of fatty acid beta-oxidation and PUFA metabolism from LA and ALA.
Sesamin, a lignan in sesame seeds and sesame seed oil, and capsaicin, the pungent principle of hot red pepper, affect lipid metabolism. Sesamin specifically inhibits delta5 desaturase activity in the Mortierella alpina fungus and rat liver microsomes, however, the effects of sesamin and capsaicin on mRNA expressions of delta6 and delta5 desaturases are not still clear. In this study, we investigated the effects of sesamin and capsaicin on the desaturation indexes of delta6 [(gamma-linolenic acid+dihomo-gamma-linolenic acid)/linolenic acid, (GLA+DGLA)/LA] and delta5 (arachidonic acid/DGLA, AA/DGLA) and mRNA expressions of delta6 and delta5 desaturases in rat primary cultured hepatocytes. To measure the mRNA expressions of delta6 and delta5 desaturase, hepatocytes were cultured in the presence of sesamin or capsaicin for 24 h. To investigate the delta6 or delta5 desaturation index, hepatocytes were cultured in the presence of LA or DGLA, respectively, with sesamin or capsaicin for 24 h. The fatty acid composition of the cells was measured by GLC. The mRNA expressions of delta6 and delta5 desaturases were detected by real time quantitative RT-PCR. Sesamin and capsaicin had no effect on the mRNA expressions of delta6 and delta5 desaturases in rat hepatocytes. Capsaicin had no effect on both delta6 and delta5 desaturation indexes, either. On the other hand, sesamin significantly reduced the index of delta5 desaturation but not delta6 desaturation. These results suggested that sesamin reduced the delta5 desaturation index without the changing of the delta5 desaturase mRNA level.
Curcumin has long been expected to be a therapeutic or preventive agent for several major human diseases because of its antioxidative, anti-inflammatory, and anticancerous effects. In phase I clinical studies, curcumin with doses up to 3600-8000 mg daily for 4 months did not result in discernible toxicities except mild nausea and diarrhea. The pharmacokinetic studies of curcumin indicated in general a low bioavailability of curcumin following oral application. Nevertheless, the pharmacologically active concentration of curcumin could be achieved in colorectal tissue in patients taking curcumin orally and might also be achievable in tissues such as skin and oral mucosa, which are directly exposed to the drugs applied locally or topically. The effect of curcumin was studied in patients with rheumatoid arthritis, inflammatory eye diseases, inflammatory bowel disease, chronic pancreatitis, psoriasis, hyperlipidemia, and cancers. Although the preliminary results did support the efficacy of curcumin in these diseases, the data to date are all preliminary and not conclusive. It is imperative that well-designed clinical trials, supported by better formulations of curcumin or novel routes of administration, be conducted in the near future.
The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells. Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.
The aim of this review has been to describe the current state of the therapeutic potential of curcumin in acute and chronic lung injuries. Occupational and environmental exposures to mineral dusts, airborne pollutants, cigarette smoke, chemotherapy, and radiotherapy injure the lungs, resulting in acute and chronic inflammatory lung diseases. Despite major advances in treating lung diseases, until now disease-modifying efficacy has not been demonstrated for any of the existing drugs. Current medical therapy offers only marginal benefit; therefore, there is an essential need to develop new drugs that might be of effective benefit in clinical settings. Over the years, there has been increasing evidence that curcumin, a phytochemical present in turmeric (Curcuma longa), has a wide spectrum of therapeutic properties and a remarkable range of protective effects in various diseases. Several experimental animal models have tested curcumin on lung fibrosis and these studies demonstrate that curcumin attenuates lung injury and fibrosis caused by radiation, chemotherapeutic drugs, and toxicants. The growing amount of data from pharmacological and animal studies also supports the notion that curcumin plays a protective role in chronic obstructive pulmonary disease, acute lung injury, acute respiratory distress syndrome, and allergic asthma, its therapeutic action being on the prevention or modulation of inflammation and oxidative stress. These findings give substance to the possibility of testing curcumin in patients with lung diseases.
Curcumin, a major active component of turmeric, is extracted from the powdered dry rhizome of Curcuma longa Linn (Zingiberaceae) and it has been used for centuries in indigenous medicine. We have shown that curcumin has a protective role against myocardial necrosis in rats. The antioxidant activity of curcumin could be attributed to the phenolic and methoxy groups in conjunction with the 1,3-diketone-conjugated diene system, for scavenging of the oxygen radicals. In addition, curcumin is shown to enhance the activities of detoxifying enzymes such as glutathione-S-transferase in vivo. We have also shown that oxygen free radicals exacerbate cardiac damage and curcumin induces cardioprotective effect and it also inhibits free-radical generation in myocardial ischemia in rats. This chapter on the cardioprotective effects of curcumin covers the following aspects: (1) the history of curcumin and its discovery as a potent drug with relevance to cardiovascular diseases; (2) mechanistic role of curcumin in vitro, emphasizing the antiplatelet and anticoagulant effects; (3) cardiovascular properties of curcumin; (4) application of curcumin in different animal models (viz. myocardial ischemia, myocardial infarction, cardiomyopathy, and arrhythmia in vitro and in vivo); (5) curcumin free-radical scavenging activity, particularly against O2 radical and depletion of the oxidative stress.
In recent years, considerable interest has been focused on curcumin a compound, isolated from turmeric. Curcumin is used as a coloring, flavoring agent and has been traditionally used in medicine and cuisine in India. The varied biological properties of curcumin and lack of toxicity even when administered at higher doses makes it attractive to explore its use in various disorders like tumors of skin, colon, duodenum, pancreas, breast and other skin diseases. This chapter reviews the data on the use of curcumin for the chemoprevention and treatment of various skin diseases like scleroderma, psoriasis and skin cancer. Curcumin protects skin by quenching free radicals and reducing inflammation through nuclear factor-KB inhibition. Curcumin treatment also reduced wound-healing time, improved collagen deposition and increased fibroblast and vascular density in wounds thereby enhancing both normal and impaired wound-healing. Curcumin has also been shown to have beneficial effect as a proangiogenic agent in wound-healing by inducing transforming growth factor-beta, which induces both angiogenesis and accumulation of extracellular matrix, which continues through the remodeling phase of wound repair. These studies suggest the beneficial effects of curcumin and the potential of this compound to be developed as a potent nontoxic agent for treating skin diseases.
Turmeric, the bright yellow spice extracted from the tuberous rhizome of the plant Curcuma longa, has been used in traditional Indian and Chinese systems of medicine for centuries to treat a variety of ailments, including jaundice and hepatic disorders, rheumatism, anorexia, diabetic wounds, and menstrual difficulties. Most of the medicinal effects of turmeric have been attributed to curcumin, the principal curcumanoid found in turmeric. Recent evidence that curcumin exhibits strong anti-inflammatory and antioxidant activities and modulates the expression of transcription factors, cell cycle proteins, and signal transducing kinases has prompted the mechanism-based studies on the potential of curcumin to primarily prevent and treat cancer and inflammatory diseases. Little work has been done to study the effect of curcumin on the development of immune responses. This review discusses current knowledge on the immunomodulatory effects of curcumin on various facets of the immune response, including its effect on lymphoid cell populations, antigen presentation, humoral and cell-mediated immunity, and cytokine production.
This overview presents curcumin as a significant chemosensitizer in cancer chemotherapy. Although the review focuses on curcumin and its analogues on multidrug resistance (MDR) reversal, the relevance of curcumin as a nuclear factor (NF)-KB blocker and sensitizer of many chemoresistant cancer cell lines to chemotherapeutic agents will also be discussed. One of the major mechanisms of MDR is the enhanced ability of tumor cells to actively efflux drugs, leading to a decrease in cellular drug accumulation below toxic levels. Active drug efflux is mediated by several members of the ATP-binding cassette (ABC) superfamily of membrane transporters, which have now been subdivided into seven families designated A through G. Among these ABC families, the classical MDR is attributed to the elevated expression of ABCB1 (Pgp), ABCC1 (MRP1), and ABCG2 (MXR). The clinical importance of Pgp, MRP1, and MXR for MDR and cancer treatment has led to the investigation of the inhibiting properties of several compounds on these transporters. At present, due in part to the disappointing results associated with the many side effects of synthetic modulators that have been used in clinical trials, current research efforts are directed toward the identification of novel compounds, with attention to dietary natural products. The advantage is that they exhibit little or virtually no side effects and do not further increase the patient's medication burden.
Curcumin, the active ingredient of turmeric (Curcuma longa) used in culinary and medical practices in Asia, has immense potential for being used in cancer chemotherapy because of its control over the cell growth regulatory mechanisms. The present chapter throws light on the role of curcumin in modulating the various phases of the cell cycle and its apoptosis-inducing effects. This is followed by a discussion on the implications of these effects of curcumin for its use as a chemotherapeutic agent in cancer. Curcumin affects various cell cycle proteins and checkpoints involving downregulation of some of the cyclins and cyclin-dependent kinases, upregulation of cdk inhibitors, and inhibition of DNA synthesis. In addition, curcumin also exerts indirect control over cell division such as inhibition of telomerase activity. Remarkably, some studies point toward a selective growth-inhibitory effect of curcumin on transformed cell lines compared to nontransformed cell lines. Curcumin has also been demonstrated to have proapoptotic effects in several in vitro studies, mostly through the mitochondria-mediated pathway of apoptosis. Curcumin-mediated regulation of apoptosis involves caspases, Bcl2 family members, inhibitors of apoptosis proteins, and heat shock proteins. The accumulating data on the in vitro and in vivo actions of curcumin together with the ongoing human clinical trials will provide a better understanding of curcumin-mediated cell growth regulation, ultimately catering to the needs of human welfare.
Curcumin possesses anti-inflammatory activity and is a potent inhibitor of reactive-oxygen-generating enzymes such as lipoxygenase/cyclooxygenase, xanthine dehydrogenase/oxidase, and inducible nitric oxide synthase (iNOS); it is an effective inducer of heme oxygenase-1. Curcumin is also a potent inhibitor of protein kinase C (PKC), EGF-receptor tyrosine kinase, and IkappaB kinase. Subsequently, curcumin inhibits the activation of NF-KB and the expressions of oncogenes including c-jun, c-fos, c-myc, NIK, MAPKs, ERK, ELK, PI3K, Akt, CDKs, and iNOS. It is considered that PKC, mTOR, and EGFR tyrosine kinase are the major upstream molecular targest for curcumin intervention, whereas the nuclear oncogenes such as c-jun, c-fos, c-myc, CDKs, FAS, and iNOS might act as downstream molecular targets for curcumin actions. It is proposed that curcumin might suppress tumor promotion through blocking signal transduction pathways in the target cells. The oxidant tumor promoter TPA activates PKC by reacting with zinc thiolates present within the regulatory domain, whereas the oxidized form of cancer chemopreventive agent such as curcumin can inactivate PKC by oxidizing the vicinal thiols present within the catalytic domain. Recent studies indicated that proteasome-mediated degradation of cell proteins play a pivotal role in the regulation of several basic cellular processes, including differentiation, proliferation, cell cycling, and apoptosis. It has been demonstrated that curcumin-induced apoptosis is mediated through the impairment of the ubiquitin-proteasome pathway.
Turmeric (Curcuma longa) is extensively used as a household remedy for various diseases. For the last few decades, work has been done to establish the biological activities and pharmacological actions of curcumin, the principle constituent of turmeric. Curcumin has proven to be beneficial in the prevention and treatment of a number of inflammatory diseases due to its anti-inflammatory activity. Arachidonic acid-derived lipid mediators that are intimately involved in inflammation are biosynthesized by pathways dependent on cyclooxygenase (COX) and lipoxygenase (LOX) enzymes. The role of LOX and COX isoforms, particularly COX-2, in the inflammation has been well established. At cellular and molecular levels, curcumin has been shown to regulate a number of signaling pathways, including the eicosanoid pathway involving COX and LOX. A number of studies have been conducted that support curcumin-mediated regulation of COX and LOX pathways, which is an important mechanism by which curcumin prevents a number of disease processes, including the cancer. The specific regulation of 5-LOX and COX-2 by curcumin is not fully established; however, existing evidence indicates that curcumin regulates LOX and COX-2 predominately at the transcriptional level and, to a certain extent, the posttranslational level. Thus, the curcumin-selective transcriptional regulatory action of COX-2, and dual COX/LOX inhibitory potential of this naturally occurring agent provides distinctive advantages over synthetic COX/LOX inhibitors, such as nonsteroidal anti-inflammatory drugs. In this review, we discuss evidence that supports the regulation of COX and LOX enzymes by curcumin as the key mechanism for its beneficial effects in preventing various inflammatory diseases.
Angiogenesis, the formation of new blood vessels from host vasculature, is critical for tumor growth and metastases. -Curcumin, a novel small-molecular-weight compound, has been shown to inhibit carcinogenesis in different organs and the common link between these actions is its antiangiogenic effect. Curcumin is a direct inhibitor of angiogenesis and also downregulates various proangiogenic proteins like vascular endothelial growth factor and basic fibroblast growth factor. Curcumin's antiangiogenic effect is also in part due to its inhibitory effect on signal transduction pathways, including those involving protein kinase C and the transcription factors NF-kappaB and AP-1. Curcumin has an inhibitory effect on two groups of proteinases involved in angiogenesis that are the members of the matrix metalloproteinase family and the urokinase plasminogen activator family. Cell adhesion molecules are upregulated in active angiogenesis and curcumin can block'this effect, adding further dimensions to curcumin's antiangiogenic effect. Curcumin shows a dose-dependent inhibition on tumor necrosis factor, a versatile cytokine, which has its effect on angiogenesis through the signal transduction pathways, expression of proangiogenic factors, and cell adhesion molecules. Curcumin's effect on the overall process of angiogenesis compounds its enormous potential as an antiangiogenic drug.
Curcumin was found to be cytotoxic in nature to a wide variety of tumor cell lines of different tissue origin. The action of curcumin is dependent on with the cell type, the concentration of curcumin (IC50: 2-40 microg/mL), and the time of the treatment. The major mechanism by which curcumin induces cytotoxicity is the induction of apoptosis. Curcumin decreased the expression of antiapoptotic members of the Bcl-2 family and elevated the expression of p53, Bax, procaspases 3, 8, and 9. Curcumin prevents the entry of nuclear factor KB (NF-KB) into the nucleus there by decreasing the expression of cell cycle regulatory proteins and survival factors such as Bcl-2 and survivin. Curcumin arrested the cell cycle by preventing the expression of cyclin D1, cdk-1 and cdc-25. Curcumin inhibited the growth of transplantable tumors in different animal models and increased the life span of tumor-harboring animals. Curcumin inhibits metastasis of tumor cells as shown in in vitro as well as in vivo models, and the possible mechanism is the inhibition of matrix metalloproteases. Curcumin was found to suppress the expression of cyclooxygenase-2, vascular endothelial growth factor, and intercellular adhesion molecule- and elevated the expression of antimetastatic proteins, the tissue inhibitor of metalloproteases-2, nonmetastatic gene 23, and Ecadherin. These results indicate that curcumin acts at various stages of tumor cell progression.
Chemoprevention, which is referred to as the use of nontoxic natural or synthetic chemicals to intervene in multistage carcinogenesis, has emerged as a promising and pragmatic medical approach to reduce the risk of cancer. Numerous components of edible plants, collectively termed "phytochemicals" have been reported to possess substantial chemopreventive properties. Curcumin, a yellow coloring ingredient derived from Curcuma longa L. (Zingiberaceae), is one of the most extensively investigated and well-defined chemopreventive phytochemicals. Curcumin has been shown to protect against skin, oral, intestinal, and colon carcinogenesis and also to suppress angiogenesis and metastasis in a variety animal tumor models. It also inhibits the proliferation of cancer cells by arresting them in the various phases of the cell cycle and by inducing apoptosis. Moreover, curcumin has a capability to inhibit carcinogen bioactivation via suppression of specific cytochrome P450 isozymes, as well as to induce the activity or expression of phase II carcinogen detoxifying enzymes. Well-designed intervention studies are necessary to assess the chemopreventive efficacy of curcumin in normal individuals as well as high-risk groups. Sufficient data from pharmacodynamic as well as mechanistic studies are necessary to advocate clinical evaluation of curcumin for its chemopreventive potential.
Curcumin is the active ingredient of turmeric that has been consumed as a dietary spice for ages. Turmeric is widely used in traditional Indian medicine to cure biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism, and sinusitis. Extensive investigation over the last five decades has indicated that curcumin reduces blood cholesterol, prevents low-density lipoprotein oxidation, inhibits platelet aggregation, suppresses thrombosis and myocardial infarction, suppresses symptoms associated with type II diabetes, rheumatoid arthritis, multiple sclerosis, and Alzheimer's disease, inhibits HIV replication, enhances wound healing, protects from liver injury, increases bile secretion, protects from cataract formation, and protects from pulmonary toxicity and fibrosis. Evidence indicates that the divergent effects of curcumin are dependent on its pleiotropic molecular effects. These include the regulation of signal transduction pathways and direct modulation of several enzymatic activities. Most of these signaling cascades lead to the activation of transcription factors. Curcumin has been found to modulate the activity of several key transcription factors and, in turn, the cellular expression profiles. Curcumin has been shown to elicit vital cellular responses such as cell cycle arrest, apoptosis, and differentiation by activating a cascade of molecular events. In this chapter, we briefly review the effects of curcumin on transcription factors NF-KB, AP-1, Egr-1, STATs, PPAR-gamma, beta-catenin, nrf2, EpRE, p53, CBP, and androgen receptor (AR) and AR-related cofactors giving major emphasis to the molecular mechanisms of its action.
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