Insulin resistance due to lipid-induced signaling defects could be prevented by mahanine

Biswas, Ashim Kumar; Bhattacharya, Sushmita; Dasgupta, Suman; Kundu, Rakesh; Roy, Sib Sankar; Pal, Buddhadev; Bhattacharya, Samir

doi:10.1007/s11010-009-0257-4

Cited by 22 publications

(12 citation statements)

References 54 publications

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“…It is suggested that, in WT mice, saturation of lipid metabolism resulting from excess dietary fat intake inhibits cellular glucose uptake and insulin signaling in peripheral tissues ( e.g. , liver, skeletal muscle, adipose), leading to insulin resistance and compensatory increase in insulin secretion (Biswas et al, 2010). Due to intrinsic defects in lipid metabolism in Gclm(−/−) mice, such a cascade of events may not occur, which may explain the sustained insulin sensitivity in HFD-fed Gclm(−/−) mice.…”

Section: Discussionmentioning

confidence: 99%

Lipid metabolism and body composition in Gclm(−/−) mice

Kendig¹,

Chen²,

Krishan³

et al. 2011

Toxicology and Applied Pharmacology

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In humans and experimental animals, high fat diets (HFD) are associated with risk factors for metabolic diseases, such as excessive weight gain and adiposity, insulin resistance and fatty liver. Mice lacking the glutamate-cysteine ligase modifier subunit gene (Gclm(−/−)) and deficient in glutathione (GSH), are resistant to HFD-mediated weight gain. Herein, we evaluated Gclm-associated regulation of energy metabolism, oxidative stress, and glucose and lipid homeostasis. C57BL/6J Gclm(−/−) mice and littermate wild-type (WT) controls received a normal diet or a HFD for 11 weeks. HFD-fed Gclm(−/−) mice did not display a decreased respiratory quotient, suggesting that they are unable to process lipid for metabolism. Although dietary energy consumption and intestinal lipid absorption were unchanged in Gclm(−/−) mice, feeding these mice a HFD did not produce excess body weight nor fat storage. Gclm(−/−) mice displayed higher basal metabolic rates resulting from higher activities of liver mitochondrial NADH-CoQ oxidoreductase, thus elevating respiration. Although Gclm(−/−) mice exhibited strong systemic and hepatic oxidative stress responses, HFD did not promote glucose intolerance or insulin resistance. Furthermore, HFD-fed Gclm(−/−) mice did not develop fatty liver, likely resulting from very low expression levels of genes encoding lipid metabolizing enzymes. We conclude that Gclm is involved in the regulation of basal metabolic rate and the metabolism of dietary lipid. Although Gclm(−/−) mice display a strong oxidative stress response, they are protected from HFD-induced excessive weight gain and adipose deposition, insulin resistance and steatosis.

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Section: Discussionmentioning

confidence: 99%

Lipid metabolism and body composition in Gclm(−/−) mice

Kendig¹,

Chen²,

Krishan³

et al. 2011

Toxicology and Applied Pharmacology

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“…Few isolated pure compounds from the MK leaf have been studied thoroughly for their details signal cross talk mechanism in different disease models including cancer 6 . For example, mahanine, a carbazole alkaloid isolated from MK leaves established its ability to combat against diabetes and the different types of cancer 7 , 8 . In a recent review 9 , we discussed in details the molecular mechanistic insight of the mahanine in different cancer model.…”

Section: Introductionmentioning

confidence: 99%

Variation in biosynthesis of an effective anticancer secondary metabolite, mahanine in Murraya koenigii, conditional on soil physicochemistry and weather suitability

Kandimalla

Das

Barge

et al. 2020

Sci Rep

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Murraya koenigii (MK) leaf being a rich source of bioactive secondary metabolites has received inordinate attention in drug development research. Formation of secondary plant metabolite(s) in medicinal plants depends on several factors and in this study the cause of variation in bioavailability and content of a vital bioactive phytochemical, mahanine in the MK leaves from different geographical locations of varying soil properties and weather parameters was determined. Accordingly, MK leaves and soil samples around the plant base in quintuplicate from each site across five states of India at similar time point were collected. Mahanine content was determined and compared among samples from different regions. The quantitative analysis data comprised that MK-leaves of southern part of India contains highest amount of mahanine, which is 16.9 times higher than that of MK-leaves of north-eastern part of India (which measured as the lowest). The results suggested that pH, conductivity and bacterial populations of the soil samples were positively correlated with mahanine content in the MK-leaves. For examples, the average soil pH of the southern India sites was in basic range (8.8 ± 0.6); whereas that of the north-east India sites was in slightly acidic ranges (6.1 ± 0.5) and mean soil conductivity value for the north east India soils was 78.3 ± 16.3 µS/cm against mean value of 432.4 ± 204.5 µs/cm for south India soils. In conclusion, this study proclaims that higher level of bioactive phytochemical, mahanine in MK leaves depending upon geographical location, weather suitability and soil’s physiochemical and microbial parameters of its cultivation sites.

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“…Leaves are a major part of Indian culinary practices with characteristics such as slight pungent odor with bitter taste regularly used for seasoning dishes [19]. Mostly roots, bark and leaves are having active bio-ingredients having antidiabetic [20], anticancer [21], antioxidant [22], hepatoprotective [23], and antilipase activities [24]. Reported important constituents are carbazole alkaloids, coumarins and flavonoids [25].…”

Section: Introductionmentioning

confidence: 99%

Mitigative Effects of Koenidine in Reducing the Toxicity Induced by Heavy Metal Lead in Human Neuroblastoma Cells

Challa¹

2016

J Chem Biol Ther

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Lead is a heavy metal been widely used in the manufacturing of glass, pigments, makeup, pipes, wine, cooking, electronic components and batteries. It is a multimedia environmental pollutant, and its exposure via different routes is found to affect metabolic functions. Primarily Lead (Pb) plays an important role in inducing oxidative stress one of the important pathologies and can affect the functioning of antioxidant defense system. The cell growth and proliferation is severely affected with the exposure of lead in designated quantities. There is no specific therapy available to treat the toxicity being generated by Pb and the efforts are on to find suitable natural biologically active components that can effectively combat the toxicity. Koenidine (KND) one of the active ingredients from the plant Murraya koenigii was considered to test its efficacy in mitigating the toxicity elicited by Pb. Human SH-SY5Y neuroblastoma cells were exposed to different concentrations (0.01-10 μM) of Pb for 48 h and the cell viability was determined. The IC50 was observed at 5 μM and this particular concentration used for further investigations. The cells were also pre-treated with KND with a range of concentration from 0-100 μM for 48 h, no change in the cell viability was observed. KND was treated (50 μM) to the cells to verify its protective effects against the pre-treatment of Pb at a concentration of 5 μM 48 h, resulted in the significant increase in the cell viability at least by 29.4% from 12.1% when compared with Pb alone treated group. Intracellular glutathione, caspase-3 and prostaglandin E2 levels were quantified to find the protective effects of koenidine. Some significant results (but less than 18%) were observed in decreasing the oxidative stress, combating apoptosis and lessening the inflammation. This clearly indicates that koenidine can be effectively used to mitigate the toxicity provoked by Pb indicating the nature of koenidine as an effective antioxidant, anti-apoptotic, and anti-inflammatory agent.

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Insulin resistance due to lipid-induced signaling defects could be prevented by mahanine

Cited by 22 publications

References 54 publications

Lipid metabolism and body composition in Gclm(−/−) mice

Lipid metabolism and body composition in Gclm(−/−) mice

Variation in biosynthesis of an effective anticancer secondary metabolite, mahanine in Murraya koenigii, conditional on soil physicochemistry and weather suitability

Mitigative Effects of Koenidine in Reducing the Toxicity Induced by Heavy Metal Lead in Human Neuroblastoma Cells

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