Medication Guide App

Corosolic Acid

Scientific Name(s): 2 alpha-hydroxy ursolic acid

Common Name(s): Glucosol , corosolic acid

Uses

Corosolic acid has numerous biological properties, including antidiabetic, anti-inflammatory, antiproliferative, and protein kinase C inhibition activity. However, there is a lack of clinical evidence to support these uses.

Dosing

Numerous commercial formulations are available, including tablets, capsules, hypoglycemic food products, and cosmetics. Most formulations are available in capsule form, containing 18% corosolic acid and derived from Lagerstroemia speciosa L. Manufacturer suggested dosage is 1 softgel by mouth 30 minutes before morning and evening meals. Softgel products are marketed for noninsulin dependent type 2 diabetic patients.

Contraindications

Avoid use with hypersensitivity to any of the plant sources of corosolic acid.

Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

Counsel patients with diabetes or those taking antidiabetic medications about potential additive effects if they are self-medicating with any oral corosolic dietary supplement.

Adverse Reactions

There is potential for skin rashes because the product may be derived from several plant species.

Toxicology

Toxicologic information regarding use in humans is lacking.

Corosolic acid is found in numerous plant species, including L. speciosa L., Tiarella polyphylla D. Don, Datisca cannabina L., Eriobotrya japonica (Thunb.) Lindl., and Perilla frutescens (L.) Britton.

History

Corosolic acid has numerous biological properties including antidiabetic, anti-inflammatory, antiproliferative, and protein kinase C inhibition activity. 1 , 2 It is found in numerous plants species, particularly L. speciosa . 3 Most medical research focuses on the compound's efficacy in diabetes. Glucosol (or GlucoFit ) is a commercially available product primarily marketed in Japan and the United States as a dietary supplement for weight loss and blood sugar balance. 1 Corosolic acid is found in numerous cosmetic products, including creams, lotions, hair tonics, as well as in hypoglycemic health foods. 3 , 4 , 5

Chemistry

Corosolic acid is a naturally occurring pentacyclic triterpene also known as 2 alpha-hydroxy ursolic acid. 6 , 7 Chemical analyses focus on the study of corosolic acid and its derivatives as inhibitors of glycogen phosphorylases for potential development of antidiabetic agents. 1 , 6 There is documented commercial interest in improving the chemical production of corosolic acid and its esters. 8 , 9

Uses and Pharmacology

Cancer
In vitro data

Corosolic acid has cytotoxic activity against several human cancer cell lines. The compound antagonized morphological modification of K-562 leukemic cells. The mechanism of action may be associated with suppression of protein kinase C activity. 10 In addition, cytotoxic activity has been documented against human cancer cell lines HL-60 (leukemia carcinoma), MCF-7 (breast carcinoma), and Hep-G2 (hepatic carcinoma). 11

Animal data

In a 2-stage Berenblum experiment on mouse skin papillomas, the inhibitory effect of corosolic acid was comparable or equivalent to beta-carotene, rosmarinic acid, and alpha-linolenic acid. 12

Diabetes

Corosolic acid may improve the insulin pathway. The action of insulin is mediated by tyrosine phosphorylation and initiated by the binding of insulin to the insulin receptor. Corosolic acid may act as an insulin sensitizer, enhancing insulin receptor B phosphorylation indirectly by inhibiting certain nonreceptor protein tyrosine phosphatases. 13 Corosolic acid may also enhance GLUT4 glucose transporter processing of glucose uptake into muscle cells. 14 Another study reported that corosolic acid inhibited gluconeogenesis by increasing the production of the gluconeogenic intermediate fructose-2,6-bisphosphate in isolated hepatocytes. Corosolic acid may promote glycolysis. 15 , 16

Animal data

Numerous animal experiments document the effect of corosolic acid on blood glucose. One study in rats found that 1% corosolic acid reduced blood glucose levels at 90 minutes after oral administration. 17 Treatment with corosolic acid lowered plasma insulin levels and reduced the blood glucose levels in KK-Ay mice 2 weeks after a single oral dose of 2 mg/kg. Blood glucose in KK-Ay mice treated with corosolic acid decreased in an insulin tolerance test. 18 Another experiment showed similar inhibitory action against increasing blood glucose levels. 19 Increasing the concentration of corosolic acid may lead to enhanced glucose uptake activity. 20 Corosolic acid induced muscle GLUT4 translocation from low-density microsomal membrane to plasma membrane in genetically-induced type 2 diabetic mice. 14 , 16

Clinical data

In a small randomized clinical trial, 10 patients with type 2 diabetes were treated with an extract from the leaves of L. speciosa standardized to 1% corosolic acid ( Glucosol ). Patients receiving Glucosol 32 or 48 mg daily for 2 weeks demonstrated a significant reduction in blood glucose levels. The softgel capsule formulation resulted in a 30% decrease, compared with 20% decrease in blood glucose levels in patients receiving the dry-powder, hard-gelatin capsule formulation. The softgel formulation has better bioavailability, and the active lipophilic triterpene ingredient is better absorbed in an oil-based, soft-gelatin capsule formulation. 21

In a study completed in Japan with 31 patients, corosolic acid lowered postchallenge plasma glucose levels. 22

Other pharmacologic activity
Chemotherapeutic

Corosolic acid enhanced the activity of treatment with tobramycin against Pseudomonas aeruginosa in a biofilm inhibition assay. 23

Inflammation

Activity against the classical pathway of the complement system is documented for corosolic acid. 24

Metabolic syndrome

In an animal model on metabolic syndrome, corosolic acid had antihypertensive, lipid-lowering, antioxidant, and anti-inflammatory effects on rats. 25 In a similar study, corosolic acid reduced blood pressure and serum-free fatty acid levels in rats. 26

Obesity

There is in vitro evidence for corosolic acid inhibiting protein tyrosine phosphatase 1B; inhibition of this phosphatase is proposed as a therapy for obesity. 27 Corosolic acid is also a pancreatic lipase inhibitor, the main enzyme for lipid absorption. 28 In a mouse study, corosolic acid acted as a peroxisome proliferator-activated receptor alpha agonist, regulating lipid metabolism and increasing fatty acid beta-oxidation in the liver. 29

Dosage

Numerous commercial formulations are available, including tablets, capsules, hypoglycemic food products, and cosmetics. Most formulations are available in capsule form containing 18% corosolic acid extracted from L. speciosa . The manufacturer suggested dosage is 1 softgel by mouth 30 minutes before morning and evening meals. Softgel products are marketed for noninsulin dependent type 2 diabetic patients. 30 , 31 , 32

Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

Counsel patients with diabetes or those taking diabetic medications about the potential additive effects if they are self-medicating with any corosolic oral dietary supplement.

Adverse Reactions

Avoid use with hypersensitivity to any source plants for corosolic acid.

Because the product may be derived from several plant species, there is a potential for skin rashes.

Toxicology

A single oral dose toxicity study in rats administered Glucosol 5 g/kg showed no marked pathological findings. 33

Bibliography

1. Wen X, Sun H, Liu J, et al. Pentacyclic triterpenes. Part 1: The first examples of naturally occurring pentacyclic triterpenes as a new class of inhibitors of glycogen phosphorylases. Bioorg Med Chem Lett . 2005;15(22):4944-4948.
2. Jung M, Park M, Lee HC, Kang YH, Kang ES, Kim SK. Antidiabetic agents from medicinal plants. Curr Med Chem . 2006;13(10):1203-1218.
3. Washino T, Kato Y, Zeida M, Minami H, inventors. Hypoglycemic banaba ( Lagerstroemia speciosa ) extracts. US patent 2005-JP7255. April 14, 2004.
4. Nojima J, Miyake Y, Ohto N, inventors. Hair cosmetics containing corosolic acid. US patent 2006-JP302560. February 14, 2006.
5. Nojima J, Miyake Y, Oto N, Dohi K, inventors; Jpn. Kokai Tokkyo Koho. Cosmetics containing corosolic acid and their uses. US patent 2006-37114. February 14, 2006.
6. Wen X, Xia J, Cheng K, et al. Pentacyclic triterpenes. Part 5: Synthesis and SAR study of corosolic acid derivatives as inhibitors of glycogen phosphorylases. Bioorg Med Chem Lett . 2007;17(21):5777-5782.
7. Aguirre MC, Delporte C, Backhouse N, et al. Topical anti-inflammatory activity of 2 alpha-hydroxy pentacyclic triterpene acids from the leaves of Ugni molinae . Bioorg Med Chem . 2006;14(16):5673-5677.
8. Takayama H, Kitajima M, Ishizuka T, Seo S, inventors. Process for producing corosolic acid. US patent 2004-866733. June 15, 2004.
9. Matsuyama F, Seino Y, Fukushima M, Miura T, Fujita T, Kaneko T, inventors. Early insulin secretion promoters containing corosolic acid and maslinic acid derivatives, and manufacture thereof. US patent 2004-JP13848. September 22, 2004.
10. Ahn KS, Hahm MS, Park EJ, Lee HK, Kim IH. Corosolic acid isolated from the fruit of Crataegus pinnatifida var. psilosa is a protein kinase C inhibitor as well as a cytotoxic agent. Planta Med . 1998;64(5):468-470.
11. Akihisa T, Kama S, Uchiyama T, et al. Cytotoxic activity of Perilla frutescens var. japonica leaf extract is due to high concentractions of oleanolic and ursolic acids. J Nat Med . 2006;60(4):331-333.
12. Banno N, Akihisa T, Tokuda H, et al. Triterpene acids from the leaves of Perilla frutescens and their anti-inflammatory and antitumor-promoting effects. Biosci Biotechnol Biochem . 2004;68(1):85-90.
13. Shi L, Zhang W, Zhou YY, et al. Corosolic acid stimulates glucose uptake via enhancing insulin receptor phosphorylation. Eur J Pharmacol . 2008;584(1):21-29.
14. Miura T, Itoh Y, Kaneko T, et al. Corosolic acid induces GLUT4 translocation in genetically type 2 diabetic mice. Biol Pharm Bull . 2004;27(7):1103-1105.
15. Yamada K, Hosokawa M, Fujimoto S, et al. Effect of corosolic acid on gluconeogenesis in rat liver. Diabetes Res Clin Pract . 2008;80(1):48-55.
16. Klein G, Kim J, Himmeldirk K, Cao Y, Chen X. Antidiabetes and anti-obesity activity of Lagerstroemia speciosa . Evid Based Complement Alternat Med . 2007;4(4):401-407.
17. Hamamoto S, Kogami H, Kohata K, Moriwaki M, Kanada H, Matsuyama F. Glucosol effect on blood glucose in rats. Yakuri to Chiryo . 1999;27(6):1075-1077.
18. Miura T, Ueda N, Yamada K, et al. Antidiabetic effects of corosolic acid in KK-Ay diabetic mice. Biol Pharm Bull . 2006;29(3):585-587.
19. Matsuyama F, Seino Y, Yamada Y, et al. Corosolic acid and its analogs as oral gluconeogenesis inhibiting agents. US patent WO2005-JP8569. April 28, 2005.
20. Zong W, Zhao G. Corosolic acid isolation from the leaves of Eriobotrta japonica showing the effects on carbohydrate metabolism and differentiation of 3T3-L1 adipocytes. Asia Pac J Clin Nutr . 2007;16(suppl 1):346-352.
21. Judy WV, Hari SP, Stogsdill WW, Judy JS, Naguib YM, Passwater R. Antidiabetic activity of a standardized extract ( Glucosol ) from Lagerstroemia speciosa leaves in Type II diabetics. A dose-dependence study. J Ethnopharmacol . 2003;87(1):115-117.
22. Fukushima M, Matsuyama F, Ueda N, et al. Effect of corosolic acid on postchallenge plasma glucose levels. Diabetes Res Clin Pract . 2006;73(2):174-777.
23. Garo E, Eldridge GR, Goering MG, et al. Asiatic acid and corosolic acid enhance the susceptibility of Pseudomonas aeruginosa biofilms to tobramycin. Antimicrob Agents Chemother . 2007;51(5):1813-1817.
24. Thuong PT, Min BS, Jin W, et al. Anti-complementary activity of ursane-type triterpenoids from Weigela subsessilis . Biol Pharm Bull . 2006;29(4):830-833.
25. Yamaguchi Y, Yamada K, Yoshikawa N, Nakamura K, Haginaka J, Kunitomo M. Corosolic acid prevents oxidative stress, inflammation and hypertension in SHR/NDmcr-cp rats, a model of metabolic syndrome. Life Sci . 2006;79(26):2474-2479.
26. Kunitomo M. Oxidative stress and atherosclerosis [in Japanese]. Yakugaku Zasshi . 2007;127(12):1997-2014.
27. Na M, Yang S, He L, et al. Inhibition of protein tyrosine phosphatase 1B by ursane-type triterpenes isolated from Symplocos paniculata . Planta Med . 2006;72(3):261-263.
28. Jang DS, Lee GY, Kim J, et al. A new pancreatic lipase inhibitor isolated from the roots of Actinidia arguta . Arch Pharm Res . 2008;31(5):666-670.
29. Yamada K, Hosokawa M, Yamada C, et al. Dietary corosolic acid ameliorates obesity and hepatic steatosis in KK-Ay mice. Biol Pharm Bull . 2008;31(4):651-655.
30. Udell RG, Hari SP, inventors. Corosolic acid formulation and its application for weight loss management and blood sugar balance. US patent 2003-640885. August 14, 2003.
31. Giampapa VC, inventor. Dietary supplement composition and method of use for enhancement of insulin sensitivity. US patent 2006-US20034. May 24, 2006.
32. Matsuyama F, inventor; Jpn Tokkyo Koho. Corosolic acid containing banaba extract for hypoglycemic foods. US patent 2004-126060. April 21, 2004.
33. Hamamoto S, Kogami H, Kohata K, Moriwaki M, Kanada H, Matsuyama F. Single oral dose toxicity of Glucosol in rats. Yakuri to Chiryo . 1999;27(6):1071-1073.

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