Cell lines

PC cells

Preparation Method

Cells were treated with Forskolin in FBS supplemented medium without exosomes and harvested at indicated times for subsequent analysis

Reaction Conditions

10 uM Forskolin, 72 hours

Applications

Forskolin is also a potent exosome biogenesis and/or secretion activator in prostate cancer (PC) cells.

Animal models

Male Wistar rats, aged 10-14 weeks old, with a mean weight of 300 g ± 50 g

Preparation Method

Forskolin (10 mg capsules) was administered orally for 8 weeks by catheter. The administered doses 6 mg/kg per day was equivalent to the 1 mg/kg per day in humans doses. Forskolin was diluted in plain water to 60 mg/100.

Dosage form

6 mg/kg per day of forskolin for 8 weeks

Applications

Forskolin predominantly decreased basal glucose in healthy rats and attenuated the severity of hyperglycemia in diabetic rats.

• Molecules, 2022, 27(3): 702.

Forskolin is a potent adenylyl cyclase activator with IC50 of 41 nM for type I adenylyl cyclase^[1]. Forskolin, with EC50 of 0.5 μM, is also an inducer of intracellular cAMP formation^[2]Forskolin induces the differentiation of a variety of cells, activates progesterone X receptor (PXR) and FXR[3] Forskolin has contractile effects on the heart, and has anti-platelet aggregation and antihypertensive effectsForskolin also induces autophagy^[4][5].

Forskolin (Coleonol) is also a potent exosome biogenesis and/or secretion activator in prostate cancer (PC) cells^[7]. Modulation of free radical stress in human red blood cell membrane by forskolin and the prospects for treatment of cardiovascular disease and Diabetes^[8].The increase in cAMP by forskolin attenuated cytotoxicity and apoptosis.

In vivo studies，forskolin predominantly decreased basal glucose in healthy rats and attenuated the severity of hyperglycemia in diabetic rats^[6]. The Mrp4(-/-) mice exhibited no overt abnormalities in the development of the retinal vasculature, but retinal vascular development in the Mrp4(-/-) mice was suppressed in response to forskolin administration.The forskolin-treated Mrp4(-/-) mice showed an increased number of Ki67-positive and cleaved caspase 3-positive ECs, a significant decrease in the amount of pericyte coverage, and a reduced number of empty sleeves^[2].

References:
[1]: Robbins JD, Boring DL, et,al. Forskolin carbamates: binding and activation studies with type I adenylyl cyclase. J Med Chem. 1996 Jul 5;39(14):2745-52. doi: 10.1021/jm960191+. PMID: 8709105.
[2]: Matsumiya W, Kusuhara S, et,al. Forskolin modifies retinal vascular development in Mrp4-knockout mice. Invest Ophthalmol Vis Sci. 2012 Dec 7;53(13):8029-35. doi: 10.1167/iovs.12-10781. PMID: 23154460; PMCID: PMC3517270.
[3]: Mayati A, Moreau A, et,al. Functional polarization of human hepatoma HepaRG cells in response to forskolin. Sci Rep. 2018 Oct 31;8(1):16115. doi: 10.1038/s41598-018-34421-8. PMID: 30382126; PMCID: PMC6208432.
[4]: Awad JA, Johnson RA, et,al. Interactions of forskolin and adenylate cyclase. Effects on substrate kinetics and protection against inactivation by heat and N-ethylmaleimide. J Biol Chem. 1983 Mar 10;258(5):2960-5. PMID: 6681815.
[5]: Seamon KB, Daly JW, et,al. Structure-activity relationships for activation of adenylate cyclase by the diterpene forskolin and its derivatives. J Med Chem. 1983 Mar;26(3):436-9. doi: 10.1021/jm00357a021. PMID: 6681845.
[6]: Ríos-Silva M, Trujillo X, et,al. Effect of chronic administration of forskolin on glycemia and oxidative stress in rats with and without experimental diabetes. Int J Med Sci. 2014 Mar 11;11(5):448-52. doi: 10.7150/ijms.8034. PMID: 24688307; PMCID: PMC3970096.
[7]: Datta A, Kim H, et,al. High-throughput screening identified selective inhibitors of exosome biogenesis and secretion: A drug repurposing strategy for advanced cancer. Sci Rep. 2018 May 25;8(1):8161. doi: 10.1038/s41598-018-26411-7. PMID: 29802284; PMCID: PMC5970137.
[8]:Niaz MA, Singh RB. Modulation of free radical stress in human red blood cell membrane by forskolin and the prospects for treatment of cardiovascular disease and diabetes. Cell Mol Biol (Noisy-le-grand). 1999 Dec;45(8):1203-7. PMID: 10643969.