Corosolic acid as future anti-diabtic, anti-obesity drug

by Nutrient Journal Editorial

Corosolic acid (2 alpha-hydroxy ursolic acid, glucosol) (Figure 1.) is a pentacyclic triterpene acid which is structurally similar to ursolic acid. Corosolic acid is usually extracted from Banaba (Lagerstroemia speciosa) leaf. It is reported to exhibit antihyperlipidemic, antioxidant, antiinflammatory, antifungal, antiviral, antineoplastic, osteoblastic and protein kinase C inhibition activity. However, there is not many clinical reports to support these claims.

Is Corosolic Acid Future Anti-diabetic Drug?

Banaba leaf extract (or corosolic acid) is typically found in supplements that help support healthy blood sugar levels and is claimed to stimulate glucose uptake and heighten insulin sensitivity.
Rats fed with 1% corosolic acid (glucosol™) exhibited significantly reduced blood glucose after 90 minutes [1]. Same formulation also exhibited significant and dose-dependent reduction in blood glucose (30% decrease after 2 weeks) over the range of 16-48 mg per day in 10 subjects with type II diabetes [2]. A study in KK-Ay mice reported dose-dependent reduction in blood glucose levels 4 h after a single oral dose (2 mg/kg) which supported the hypotesis that corosolic acid improves glucose metabolism by reducing insulin resistance [3]. A 12% decrease in fasting blood glucose was reported in 12 non-diabetic subjects who were given 10 mg of corosolic acid (as banaba extract standardized to 18% corosolic acid) for 2 weeks [4]. In an unpublished study by Xu (mentioned in a review by Stohs et al. [5]) subjects received soft gel caps containing 10 mg of corosolic acid. Both fasting and 2h post-prandial blood glucose levels decreased by 10% compared to placebo group [5]. In Fukushima et al. study [6] 31 subjects were given 10 mg corosolic acid (99% pure) or placebo 5 minutes after 75 g of glucose tolerance test. It has been reported that corosolic acid reduced blood glucose levels from 60 to 120 minutes, with highest difference at 90 minutes.

Cholesterol

In patients with type II diabetes mellitus intestinal cholesterol synthesis and cholesterol esterification is increased [7]. Corosolic acid has been show to reduce cholesterol absorption process in the small intestine via inhibition of activity of cholesterol acyltransferase [8].
Mechanisms of Action

Corosolic acid is suggested to induce GLUT4 translocation [9,10]. Translocation of more GLUT4 glucose transporters to the cell surface means increased insulin action [11]. Disrupted GLUT4 gene has been shown to cause insulin resistance in skeletal muscles as well as diabetes [12]. Corosolic acid also works as “insulin sensitizer” by inhibiting enzymatic activities of several diabetes-related non-receptor protein tyrosine phosphatases (such as PTP1B) which indirectly enhances insulin receptor B phosphorylation [9]. Inhibition of protein tyrosine phosphatase 1B is an attractive target for treatment of diabetes and obesity [13,14]. Corosolic acid also promotes glycolysis [5] and suppresses gluconeogenesis (via increased production of fructose-2,6-bisphosphate) [15].

Figure 1. Corosolic aicd.

Advantage of corosolic acid in treatment of diabetes is that unlike insulin treatment it does not increase anti-insulin antibody production [16].

“Fat Burning” Properties of Corosolic Acid

In twelve subjects who were taking banaba extract for 2 weeks an average three pound weight loss was reported [4]. Corosolic acid has also been shown to retard the absorption of fatty acid via inhibition of pancreatic lipase enzyme (enzyme responsible for lipid absorption) [17].
Cortisol Management

Corosolic acid is a potent and selective inhibitor of the enzyme (11-beta hydroxysteroid dehydrogenase type 1) that converts inactive cortisone to active cortisol [18]. Therefore, corosolic acid may prevent excessive cortisol production.
Corosolic Acid Safety and Dosage

No animal studies have been designed to assess toxicity or LD50 (median lethal dose) values for corosolic acid or banaba extracts. No adverse effects have been observed or reported in animal studies or controlled human clinical trials [5], however information about toxicity in human subjects is lacking.

Various commercially available formulations are available including softgels, tablets, capsules, powders and cosmetics. Banaba (Lagerstroemia speciosa) leaf extracts usually contain from 1 to 18% of corosolic acid. It appears that corosolic acid is better absorbed in oil-based soft gelatin formulation compared to dry powder [2]. Typical recommended dose (by manufacturers) is 1 capsule 20 to 30 minutes with or before morning and evening meals (some times even 3 times daily). Effects of corosolic acid are dose-dependent [2,3], however more human studies assessing proper dose are warranted.

References

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