Malaysian Applied Biology Journal

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46_04_17

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Malays. Appl. Biol. (2017) 46(4): 145–152

Tinospora crispa METHANOLIC CRUDE EXTRACT ACTIVATES

APOPTOTIC PATHWAY OF INSULIN RESISTANT-HEPG2 CELL

LINES BY IMPROVING THE INSULIN SENSITIVITY

 

MOHD NAZRI ABU1*, HAMZAH FANSURI HASSAN1, ROSMADI YUSOFF2

and WAN IRYANI WAN ISMAIL2,3

 

1Faculty of Health Sciences, Universiti Teknologi MARA,

Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia

2Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus,

42300 Bandar Puncak Alam, Selangor, Malaysia

3School of Fundamental Science, Universiti Malaysia Terengganu,

21030 Kuala Nerus, Terengganu, Malaysia


*Email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it

 

Accepted 29 November 2017, Published online 31 December 2017

 

ABSTRACT

This study elucidates the growth inhibition of the insulin resistant-human hepatocellular carcinoma (IR-HepG2) cell lines after treating with Tinospora crispa methanolic crude extract. The IR-HepG2 cell lines were cultured in high glucose-insulin medium, subsequently established by the radiolabelled 2-deoxyglucose assay. The IR-HepG2 (negative control) and WRL68 (normal control) were treated with T. crispa methanolic crude extract and rosiglitazone malate (RM-positive control) respectively. The glucose uptake, downregulated IGF-1R and Bcl-2 protein, and apoptosis mechanism were determined using the immunoblotting method and transmission electron microscope (TEM). Glucose uptake was decreased in IR-HepG2 cell lines, while increased after treated with T. crispa methanolic crude extract and RM. The protein expressions of IR-HepG2 treated with T. crispa was significantly increased (p < 0.05) the insulin receptor (InsR), p-Akt, and GLUT4. IR-HepG2 cell lines stimulated with insulin and treated with T. crispa crude extract were found to activate the apoptosis pathway through the expression of caspases-3, 8, 9 and Bad. Ultimately, the growth of IR-HepG2 cell lines was inhibited via apoptosis after improving cell sensitivity towards insulin and its glucose uptake. Nevertheless, mechanism of T. crispa to induce the effects is still unclear either as a direct ligand or as a cofactor, and it requires further investigations.

Key words: Tinospora crispa, insulin resistance, insulin resistant-HepG2, apoptosis, cell culture, TEM

 

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