Pharmacological Activities of Natural Triterpenoids and Their Therapeutic Implications

Džubák, Petr; Hajdúch, Marián; Vydra, David; Hustova, Alica; Kvasnica, Miroslav; Biedermann, David; Marková, Lenka; Urban, Milan; Šarek, Jan

doi:10.1002/chin.200637244

Cited by 87 publications

(118 citation statements)

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“…Accordingly, the search for more effective and safer natural bio-molecules, with the dual ability to decrease glucose absorption and reduce oxidative damage, has become an important scientific goal. Oleanolic acid (OA) (3β-hydroxy-olean-12-en-28-oic acid), a pentacyclic triterpene widely distributed in the plant kingdom, has attracted the attention of researchers for its interesting pharmacological properties (Liu, 2005;Dzubak et al, 2006), including anti-diabetic activity (Castellano et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Free radical scavenging and α-glucosidase inhibition, two potential mechanisms involved in the anti-diabetic activity of oleanolic acid

et al. 2016

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SUMMARY:This work investigates the role of oleanolic acid (OA), isolated from the olive (Olea europaea L.) leaf, as a radical scavenger and inhibitor of the hydrolyzing enzymes of dietary carbohydrates. New evidence is provided showing that OA may capture 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) and peroxyl radicals, and also exert a strong and non-competitive inhibition of α-glucosidase (IC 50 10.11 ± 0.30 µM). The kinetic and spectrometric analyses performed indicate that OA interacts with this enzyme inside a hydrophobic pocket, through an endothermic and non spontaneous process of a hydrophobic nature. These are two possible mechanisms by which OA may facilitate a better control of post-prandial hyperglycaemia and oxidative stress, so contributing to preserving insulin signalling. Obesity, insulin resistance and Type 2 Diabetes Mellitus are considered the first pandemics of the 21st century. In this sense, OA might be used in future preventive and therapeutic strategies, as an ingredient in new drugs and functional foods.KEYWORDS: Anti-diabetic activity; Antioxidant; α-glucosidase inhibitor; Olea europaea; Oleanolic acid RESUMEN: La Captación de radicales libres y la inhibición de α-glucosidasa, dos posibles mecanismos involucrados en la actividad antidiabética del ácido oleanólico. Este trabajo estudia el papel del ácido oleanólico (OA), aislado de la hoja de olivo, como secuestrador de radicales libres e inhibidor de enzimas implicados en la hidrolisis de los carbohidratos de la dieta, dos mecanismos por los que el triterpeno podría mitigar la hiperglicemia postprandial y el estrés oxidativo. Se aportan nuevas evidencias que muestran que el OA puede capturar radicales ácido 2,2'-azino-bis-(3-etilbenzotiazolín)-6-sulfónico y peroxilo, y que ejerce una potente inhibición nocompetitiva de α-glucosidasa (IC 50 10.11±0.30 µM). El análisis cinético y espectrométrico llevado a cabo indica que OA interacciona con este enzima en el interior de un bolsillo hidrofóbico, mediante un proceso endotér-mico no espontáneo, de naturaleza hidrofóbica. Estos son dos posibles mecanismos por los cuales el OA puede facilitar un mejor control de la hiperglucemia postprandial y el estrés oxidativo, lo que contribuye a preservar la señalización de la insulina. La obesidad, la resistencia a la insulina y la diabetes mellitus tipo 2 se consideran la primera pandemia del siglo XXI. En este sentido, el OA podría ser utilizado en futuras estrategias preventivas y terapéuticas, como ingrediente de nuevos fármacos y alimentos funcionales. Free radical scavenging and α-glucosidase inhibition, two potential mechanisms involved in the anti-diabetic activity of oleanolic acid. Grasas Aceites 67 (3): e142. doi: http://dx

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Section: Introductionmentioning

confidence: 99%

Free radical scavenging and α-glucosidase inhibition, two potential mechanisms involved in the anti-diabetic activity of oleanolic acid

et al. 2016

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“…1,2 Many factors play signicant roles in the processes of cancer development. [3][4][5][6][7][8] Simultaneously, there is an increasing number of patents being issued in order to protect new triterpenoid compounds with biological, mainly anticancer and antiviral (including anti-HIV), effects. However, there are many other reasons why cancer is so prevalent.…”

Section: Introductionmentioning

confidence: 99%

Pentacyclic triterpenoids with nitrogen- and sulfur-containing heterocycles: synthesis and medicinal significance

et al. 2015

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Triterpenoids are natural compounds with a variety of biological activities and are usually produced by plants as secondary metabolites. In recent decades, scientists focused on the properties of triterpenoids have discovered many activities, such as antitumor, antiviral, antimicrobial, anti-inflammatory and others. Thousands of new triterpenoids with various skeletal modifications have now been synthesized. One of the most important modifications is the formation of a new heterocyclic ring. The simple fact that the vast majority of currently used drugs are heterocyclic compounds has encouraged a lot of researches to synthesize analogous triterpenoid derivatives in order to find new molecules with higher activities and consequently optimize their pharmacological profile. The biological properties of triterpenoid heterocycles are very promising and many of them have been studied, especially as antitumor agents. This review is mainly focused on the synthesis of various types of nitrogen and occasionally sulfur-containing heterocyclic triterpenoids for their potential use as future drugs in medicine and in addition discusses their overall biological activities.

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“…Thus, clinical development of plant derived flavonoids and phenolic/polyphenolic antioxidants as chemopreventive agents could significantly reduce disease-related morbidity and mortality and improve prognosis. Triterpenes or triterpenoids are members of a larger family of structurally related compounds known as cyclosqualenoids that are widely distributed in the plant kingdom [5]. Oleanolic acid and ursolic acid are naturally occurring triterpenoids that have been used in traditional medicine for centuries as antibacterial, antifungal, anti-cancer, and anti-inflammatory agents [6–8].…”

Section: Introductionmentioning

confidence: 99%

Oleanane triterpenoid CDDO-Me inhibits growth and induces apoptosis in prostate cancer cells through a ROS-dependent mechanism

Deeb

Gao

Jiang

et al. 2010

Biochemical Pharmacology

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CDDO-Me, a synthetic triterpenoid derived from oleanolic acid, is a promising anticancer agent that has shown strong activity against a wide variety cancer types in vitro and in vivo. We have previously shown that CDDO-Me induces apoptosis in prostate cancer cells irrespective of their hormonal status. To further understand the proapoptotic mechanism of CDDO-Me, we investigated the role of reactive oxygen species (ROS) in mediating the apoptosis inducing activity of CDDO-Me in LNCaP and PC-3 prostate cancer cell lines. Here, we show that CDDO-Me induces ROS generation from both nonmitochondrial and mitochondrial sources, which is associated with induction of apoptosis as characterized by increased annexin V-binding, cleavage of PARP-1 and procaspases -3,-8, -9, loss of mitochondrial membrane potential and release of cytochrome c. In addition, CDDO-Me inhibited cell survival Akt, NF-κB and mTOR signaling proteins. The inhibition of ROS generation by N-acetylcysteine (NAC) or by overexpression of antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase1 (SOD1) prevented CDDO-Me-induced apoptosis. Pretreatment with NAC blocked annexin V-binding, cleavage of PARP-1 and procaspases -3,-8, -9, loss of mitochondrial membrane potential and release of cytochrome c by CDDO-Me. NAC also prevented the inhibition of constitutively active Akt, NF-κB and mTOR by CDDO-Me. Together, these data indicate that ROS plays an essential role in induction of apoptosis by CDDO-Me in prostate cancer cells.

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Pharmacological Activities of Natural Triterpenoids and Their Therapeutic Implications

Abstract: HAJDUCH, M.; VYDRA, D.; HUSTOVA, A.; KVASNICA, M.; BIEDERMANN, D.; MARKOVA, L.; URBAN, M.; SAREK*, J.; Nat. Prod. Rep. 23 (2006) 3, 394-411; Dep. Org. Nucl. Chem., Charles Univ., CZ-128 40 Prague 2, Czech Republic; Eng.) -Lindner 37-244

Cited by 87 publications

References 1 publication

Free radical scavenging and α-glucosidase inhibition, two potential mechanisms involved in the anti-diabetic activity of oleanolic acid

Free radical scavenging and α-glucosidase inhibition, two potential mechanisms involved in the anti-diabetic activity of oleanolic acid

Pentacyclic triterpenoids with nitrogen- and sulfur-containing heterocycles: synthesis and medicinal significance

Oleanane triterpenoid CDDO-Me inhibits growth and induces apoptosis in prostate cancer cells through a ROS-dependent mechanism

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