Transdermal delivery of Syzygium aromaticum-derived oleanolic acid by dermal patches in STZ-induced diabetic rats.

Background. Sustained hyperglycaemia leads to the development of haematological alterations which, if left untreated, is associated with cardiovascular complications. Insulin is the mainstay drug in type 1 diabetes mellitus (T1D); however, the use of insulin is associated with haematological alterations that could further worsen cardiovascular complications. Therefore, the aim of the study was to investigate the haematological effects of oleanolic acid (OA) in streptozotocin- (STZ-) induced diabetic rats. Methods. The animals were separated into five groups; the nondiabetic group (ND), the diabetic control group (DC), and the treatment groups of insulin (170 μg/kg, s.c), metformin (500 mg/kg, p.o), and OA (80 mg/kg, p.o). OA was administered orally twice a day. Thereafter, the animals were sacrificed, and blood and tissues were collected for haematological, hormonal, and oxidative status analysis. Results. Untreated diabetic rats exhibited hyperglycaemia, elevated glycated haemoglobin (HbA1c), oxidative stress, and a reduced erythropoietin (EPO) concentration when compared to ND rats. However, administration of OA attenuated hyperglycaemia, HbA1c, and EPO concentrations compared to DC rats. The reduction of blood glucose concentration, HbA1c, and improved EPO concentrations was further associated with a notable increase in red blood cell (RBC) count and other RBC indices. We also observed an increase in the antioxidant status of the RBCs with a concomitant decrease in oxidative stress. Conclusion. These findings suggest that OA improves diabetes-induced haematological changes caused by hyperglycaemia and attenuates the progression of cardiovascular complications in DM individuals.

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Plant-derived oleanolic acid ameliorates markers of subclinical inflammation and innate immunity activation in diet-induced pre-diabetic rats

Therapeutic Advances in Endocrinology and Metabolism ◽

10.1177/2042018820935771 ◽

2020 ◽

Vol 11 ◽

pp. 204201882093577

Author(s):

Mlindeli Gamede ◽

Lindokuhle Mabuza ◽

Phikelelani Ngubane ◽

Andile Khathi

Keyword(s):

Cell Count ◽

Oleanolic Acid ◽

Proinflammatory Cytokines ◽

Immune Activation ◽

Molecular Mechanisms ◽

Dietary Intervention ◽

Immune Cell ◽

Diabetic Rats ◽

Sprague Dawley ◽

Cell Counts

Aims: Sub-clinical inflammation during pre-diabetes is one of the predisposing factors that facilitates the progression of pre-diabetes to type 2 diabetes. The administration of oleanolic acid (OA) with or without dietary intervention ameliorates the metabolic and cardiovascular complications in diet-induced pre-diabetes animal models of pre-diabetes. This study aimed to investigate whether OA can also suppress immune activation and ameliorate pro-inflammatory markers. Methods: Pre-diabetes was induced by feeding Sprague Dawley rats a high-fat high carbohydrate diet for 20 weeks. The pre-diabetic rats were then treated with OA (80 mg/kg) or metformin (500 mg/kg) in the presence or absence of dietary interventions for a period of 12 weeks. At the end of the treatment period, the animals were euthanised and whole blood was used for platelet and immune cell count while plasma was used for fibrinogen, cluster differentiation 40 ligand and pro-inflammatory cytokine evaluation. Results: The results of this study revealed that OA, with or without dietary intervention, improved lipid metabolism by restoring high-density lipoprotein (HDL) and low-density lipoproteins (LDLs) as well as reducing platelets and immune cell counts. Furthermore, OA also decreased plasma proinflammatory cytokines, including tumour necrosis factor-α and -1β. Markers of immune activation such as C-reactive protein, fibrinogen, and CD40L were also decreased upon administration of OA with or without dietary intervention. Conclusion: The findings of this study suggest that OA may provide an alternative to prevent the progression of pre-diabetes to overt diabetes. This was evident by the reduction of differential white blood cell count and proinflammatory cytokines that exercebate insulin resistance. However, more studies are needed to elucidate the molecular mechanisms and to improve efficacy.

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Molecular Mechanism Underlying the Antidiabetic Effects of a Siddha Polyherbal Preparation in the Liver of Type 2 Diabetic Adult Male Rats

Journal of Evidence-Based Complementary & Alternative Medicine ◽

10.1177/2156587212460047 ◽

2012 ◽

Vol 18 (1) ◽

pp. 29-42 ◽

Cited By ~ 1

Author(s):

Venkataraman Balaji ◽

Jayaraman Selvaraj ◽

Sampath Sathish ◽

Chinnaiyan Mayilvanan ◽

Karundevi Balasubramanian

Keyword(s):

Insulin Receptor ◽

Molecular Mechanism ◽

Diabetic Rats ◽

Male Rats ◽

Tinospora Cordifolia ◽

Syzygium Aromaticum ◽

Mrna Levels ◽

Type 2 Diabetic ◽

Antidiabetic Effects

A siddha polyherbal preparation consisting of 5 medicinal plants, namely, Asparagus racemosus, Emblica officinalis, Salacia oblonga, Syzygium aromaticum, and Tinospora cordifolia, in equal ratio, was formulated to examine the molecular mechanism by which it exhibits antidiabetic effects in the liver of high-fat and fructose-induced type 2 diabetic rats. The polyherbal preparation treated type 2 diabetic rats showed an increase in insulin receptor, Akt, and glucose transporter2 mRNA levels compared with diabetic rats. Insulin receptor, insulin receptor substrate-2, Akt, phosphorylated Akt substrate of 160kDaThreonine642, α-Actinin-4, β-arrestin-2, and glucose transporter2 proteins were also markedly decreased in diabetic rats, whereas the polyherbal preparation treatment significantly improved the expression of these proteins more than that of metformin-treated diabetic rats. The expression pattern of insulin signaling molecules analyzed in the present study signifies the therapeutic efficacy of the siddha polyherbal preparation.

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Semisynthesis of Derivatives of Oleanolic Acid fromSyzygium aromaticumand Their Antinociceptive and Anti-Inflammatory Properties

Mediators of Inflammation ◽

10.1155/2016/8401843 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 8

Author(s):

Sibusiso Rali ◽

Opeoluwa O. Oyedeji ◽

Olukayode O. Aremu ◽

Adebola O. Oyedeji ◽

Benedicta N. Nkeh-Chungag

Keyword(s):

Oleanolic Acid ◽

Acetyl Derivative ◽

Syzygium Aromaticum ◽

Analgesic Effects ◽

Pentacyclic Triterpenoid ◽

Ft Ir ◽

Anti Inflammatory ◽

Pain Test ◽

Layer Chromatography ◽

Derivatives Of

Oleanolic acid is a pentacyclic triterpenoid compound widely found in plants and well known for its medicinal properties. Oleanolic acid (OA) was isolated from the ethyl acetate extract ofSyzygium aromaticumflower buds. Semisynthesis afforded both acetate and ester derivatives. The derived compounds were monitored with thin layer chromatography and confirmed with nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), Fourier infrared (FT-IR) spectroscopy, and melting point (Mp). All these compounds were evaluated for their analgesic and anti-inflammatory properties at a dose of 40 mg/kg. Significant analgesic and anti-inflammatory effects were noted for all OA-derived compounds. In the formalin-induced pain test, the derivatives showed better analgesic effects compared to their precursor, whereas, in the tale flick test, oleanolic acid proved to be superior in analgesic effects compared to all its derivatives with the exception of the acetyl derivative. Acute inflammatory tests showed that acetyl derivatives possessed better anti-inflammatory activity compared to the other compounds. In conclusion, semisynthesis of oleanolic acid yielded several derivatives with improved solubility and enhanced analgesic and anti-inflammatory properties.

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