Symplocos cochinchinensis enhances insulin sensitivity via the down regulation of lipogenesis and insulin resistance in high energy diet rat model.
BACKGROUND
This plant has been utilized in Indian system of medicine for treatment of diabetes. This is clearly evident from the composition of Ayurvedic preparation for diabetes 'Nisakathakadi Kashayam' where this is one of the main ingredients of this preparation AIM OF THE STUDY: The study aims in elucidating the molecular mechanisms underlying the insulin sensitizing effects of Symplocos cochinchinensis ethanol extract (SCE) using a high fructose and saturated fat (HFS) fed insulin resistant rat model.


METHODS
Experimental groups consisted of normal diet (ND), ND+SCE 500mg/kg bwd, HFS+vehicle, HFS+metformin 100mg/kg bwd, HFS+SCE 250/500mg/kg bwd. Initially the animals were kept under HFS diet for 8 weeks, and at the end of 8 week period, animals were found to develop insulin resistance and dyslipidemia. Post-administration of SCE, metformin or vehicle were carried out for 3 weeks. Gene and protein expressions relevant to insulin signalling pathway were analysed.


RESULTS
HFS significantly altered the normal physiology of animals via proteins and genes relevant to metabolism like stearoyl-CoA desaturase (SCD1), sterol regulatory element binding protein 1 (SREBP-1c), fatty acid synthase (FAS), glucose 6 phosphatase (G6Pase), phosphoenol pyruvate carboxykinase (PEPCK), glucose transporter 2 (GLUT2), protein tyrosine phosphatse 1B (PTP1B), peroxisome proliferator activated receptor alpha (PPAR alpha), sirtuin 1 (SIRT1) and glucokinase. SCE administration attenuates the insulin resistance in HFS rat by the down regulation of SCD1 gene expression that modulates SREBP-1c dependent and independent hepatic lipid accumulation.


CONCLUSIONS
SCE enhances insulin sensitivity via the down regulation of lipogenesis and insulin resistance in HFS rat model.
Agroprocessing and Natural Products Division, CSIR - National Institute for Interdisciplinary Science and Technology(NIIST), Thiruvananthapuram 695019, Kerala, India.
Kalathookunnel Antony
KA
Antu
Agroprocessing and Natural Products Division, CSIR - National Institute for Interdisciplinary Science and Technology(NIIST), Thiruvananthapuram 695019, Kerala, India.
Mariam Philip
MP
Riya
Agroprocessing and Natural Products Division, CSIR - National Institute for Interdisciplinary Science and Technology(NIIST), Thiruvananthapuram 695019, Kerala, India.
Anupama
A
Nair
Division of Biochemistry, CSIR - Central Drug Research Institute(CDRI), Sector 10, Janakipuram Extension, Sitapur Road, Lucknow 226031, Uttar Pradesh, India.
Arvind
A
Mishra
Division of Biochemistry, CSIR - Central Drug Research Institute(CDRI), Sector 10, Janakipuram Extension, Sitapur Road, Lucknow 226031, Uttar Pradesh, India.
Arvind K
AK
Srivastava
Agroprocessing and Natural Products Division, CSIR - National Institute for Interdisciplinary Science and Technology(NIIST), Thiruvananthapuram 695019, Kerala, India. Electronic address: raghukgopal@niist.res.in.
Kozhiparambil Gopalan
KG
Raghu
D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D059305:Diet, High-Fat; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D000431:Ethanol / Q000737:chemistry; D005632:Fructose; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D050155:Lipogenesis / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D019684:Magnoliopsida / Q000737:chemistry*; D008297:Male; D008687:Metformin / Q000494:pharmacology; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000737:chemistry; D013997:Time Factors
D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D012997:Solvents; D005632:Fructose; D000431:Ethanol; D008687:Metformin
Chloroform (PubChem CID: 6212); Diabetes; Ethanol (PubChem CID: 702); Glucose (PubChem CID: 5793); Glycine (PubChem CID: 750); Hepatic steatosis; Insulin resistance; Metformin (PubChem CID: 14219); Methanol (PubChem CID: 887); SCD1; SDS (PubChem CID: 3423265); SIRT1; Sodium chloride (PubChem CID: 5234); Symplocos cochinchinensis