A Lanosteryl Triterpene from Protorhus longifolia Improves Glucose Tolerance and Pancreatic Beta Cell Ultrastructure in Type 2 Diabetic Rats

Mabhida, Sihle E.; Mosa, Rebamang A.; Penduka, Dambudzo; Osunsanmi, Foluso Oluwagbemiga; Dludla, Phiwayinkosi V.; Djarova, Trayana; Opoku, Andy R.

doi:10.3390/molecules22081252

Cited by 15 publications

(18 citation statements)

References 32 publications

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“…The formalin fixed tissues were routinely processed by a Leica TP 1020 automated processor (Leica Biosystems, Buffalo Grove, IL, USA) and embedded in paraffin wax. Tissues were sectioned and attached to aminopropyltriethoxysilane coated glass slides, after which they were stained with hematoxylin and eosin [ 15 ]. Examination of the slides was performed by an independent Pathologist without prior knowledge of the experimental groups (Vet Diagnostix Laboratories, Pietermaritzburg, South Africa).…”

Section: Methodsmentioning

confidence: 99%

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A Lanosteryl triterpene from Protorhus longifolia augments insulin signaling in type 1 diabetic rats

Mabhida

Johnson

Ndlovu

et al. 2018

BMC Complement Altern Med

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BackgroundA substantial literature supports antidiabetic properties of the lanosteryl triterpene (methyl-3β-hydroxylanosta-9,24-dien-21-oate, RA-3) isolated from Protorhus longifolia stem bark. However, the molecular mechanism(s) associated with the antihyperglycemic properties of the triterpene remained to be explored. The current study aimed at investigating the molecular mechanism(s) through which RA-3 improves insulin signaling in streptozotocin-induced type 1 diabetic rats.MethodsThe type 1 diabetic rats were treated daily with a single oral dose of RA-3 (100 mg/kg) for 28 days. The rats were then sacrificed, and blood, skeletal muscle and pancreases were collected for biochemical, protein expression and histological analysis, respectively.ResultsPersistently high blood glucose levels in the diabetic control rats significantly increased expression of IRS-1Ser307 while the expression of p-Akt Ser473, p-GSK-3β Ser9, GLUT 4 and GLUT 2 were decreased. However, enhanced muscle insulin sensitivity, which was indicated by a decrease in the expression of IRS-1ser307 with a concomitant increase in the p-AktSer473, p-GSK-3β Ser9, GLUT 4 and GLUT 2 expression were observed in the diabetic rats treated with RA-3. The triterpene-treated animals also showed an improved pancreatic β-cells morphology, along with increased C-peptide levels. An increase in the levels of serum antioxidants such as catalase, superoxide dismutase, and reduced glutathione was noted in the rats treated with the triterpene, while their serum levels of interleukin-6 and malondialdehyde were reduced.ConclusionsIt is apparent that RA-3 is able to improve the insulin signaling in type 1 diabetic rats. Its beta (β)-cells protecting mechanism could be attributed to its ability to alleviate inflammation and oxidative stress in the cells.

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Section: Methodsmentioning

confidence: 99%

“…Engl. (Anacardiaceae) stem bark has been reported to possess hypoglycemic properties, which are also associated with stimulation of cellular glucose uptake [ 13 ] and improved glucose tolerance [ 14 , 15 ]. However, the molecular mechanism(s) associated with these antidiabetic properties of the compound remained to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

A Lanosteryl triterpene from Protorhus longifolia augments insulin signaling in type 1 diabetic rats

Mabhida

Johnson

Ndlovu

et al. 2018

BMC Complement Altern Med

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“…Furthermore, despite the ROS-mediated renal toxicity of gentamicin and adenine, the improved serum total antioxidant status, GSH and SOD along with reduced MDA content in the rats treated with RA-3 indicated its tissue protective potential against oxidative damage. It is interesting to note from these results that the ability of RA-3 to enhance endogenous antioxidant defense while inhibiting lipid peroxidation has previously been demonstrated in streptozotocin (STZ)-induced diabetes and isoproterenol (ISO)-induced myocardial injury in rat models [ 15 , 16 ]. It is also worth noting that similar to gentamicin induced renal tubular toxicity, the necrotic toxicity of STZ and ISO are also associated with oxidative stress [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…Fresh working solutions of RA-3 (50 and 100 mg/kg body weight) were prepared in 2% Tween 20. These concentrations were based on our previous studies on the compound [ 14 , 15 , 16 ].…”

Section: Methodsmentioning

confidence: 99%

“…There is substantial evidence on potential role of various medicinal plants, as crude extracts or pure isolated compounds [ 2 , 11 , 12 , 13 ], in protecting the kidney from various insults thus, maintaining its integrity and functions. Even though methyl-3β-hydroxylanosta-9,24-dien-21-oate (RA-3), a lanosteryl triterpene from Protorhus longifolia (Bernh) Engl., has displayed significant various bioactivities such as antihyperlipidemic [ 14 ], antihyperglycemic [ 15 ], and cardioprotective [ 16 ] effects, its nephroprotective potential has not been reported. However, the triterpenes from this plant have previously exhibited lack of cytotoxic effects on human embryonic kidney cell lines [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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A Lanosteryl Triterpene (RA-3) Exhibits Antihyperuricemic and Nephroprotective Effects in Rats

et al. 2020

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Considering the global health threat posed by kidney disease burden, a search for new nephroprotective drugs from our local flora could prove a powerful strategy to respond to this health threat. In this study we investigated the antihyperuricemic and nephroprotective potential of RA-3, a plant-derived lanosteryl triterpene. The antihyperuricemic and nephroprotective effect of RA-3 was investigated using the adenine and gentamicin induced hyperuricemic and nephrotoxicity rat model. Following the induction of hyperuricemia and nephrotoxicity, the experimental model rats (Sprague Dawley) were orally administered with RA-3 at 50 and 100 mg/kg body weight, respectively, daily for 14 days. Treatment of the experimental rats with RA-3, especially at 100 mg/kg, effectively lowered the serum renal dysfunction (blood urea nitrogen and creatinine) and hyperuricemic (uric acid and xanthine oxidase) biomarkers. These were accompanied by increased antioxidant status with decrease in malondialdehyde content. A much improved histomorphological structure of the kidney tissues was also observed in the triterpene treated groups when compared to the model control group. It is evident that RA-3 possesses the antihyperuricemic and nephroprotective properties, which could be vital for prevention and amelioration of kidney disease.

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Pancreatic inflammation induced by hypothyroidism in female rabbits is associated with cholesterol accumulation and a reduced expression of CYP51A1, FXRβ, and PPARβ/δ

Rojas‐Juárez,

Rodríguez‐Castelán,

Cuatecontzi‐Fuentes

et al. 2024

The Anatomical Record

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In women and animal models, hypothyroidism induces hypercholesterolemia, pancreatitis, and insulitis. We investigated whether lipids are involved in the effects of hypothyroidism in the pancreas. Control (n = 6) and hypothyroid (n = 6) adult female rabbits were used. We quantified serum and pancreatic triacylglycerol and total cholesterol levels, the oxidative and antioxidant status, and the expression of low‐density lipoprotein cholesterol receptor (LDLR) in the pancreas. Inflammation of the pancreas was evaluated by infiltration of immune cells positive to CD163 and α‐farnesoid receptor (FXRα). Other lipid players involved in both inflammation and insulin secretion of the pancreas, such as lanosterol 14‐α‐demethylase (CYP51A1), β‐farnesoid receptor (FXRβ), 3β‐hydroxysteroid dehydrogenase (3β‐HSD), and peroxisome proliferator‐activated receptor β (PPARβ/δ), were quantified. Groups were compared by t‐Student or U‐Mann–Whitney tests (p ≤ 0.05). Hypothyroidism induced hypercholesterolemia and a high cholesterol accumulation in the pancreas of female rabbits, without affecting oxidative or antioxidative status nor the expression of LDLR. The pancreas of hypothyroid females showed inflammation identified by a great infiltration of immune cells, macrophages CD163+, and loss of expression of FXRα+ in immune cells. Moreover, a reduced expression of CYP51A1, FXRβ, and PPARβ/δ, but not 3β‐HSD, in the hypothyroid pancreas was found. Pancreatitis and insulitis promoted by hypothyroidism may be related to the accumulation of cholesterol, lanosterol actions, and the activation of PPARβ/δ. All inflammatory markers evaluated in this study are related to glucose regulation, suggesting the link between hypothyroidism and diabetes.

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A Lanosteryl Triterpene from Protorhus longifolia Improves Glucose Tolerance and Pancreatic Beta Cell Ultrastructure in Type 2 Diabetic Rats

Cited by 15 publications

References 32 publications

A Lanosteryl triterpene from Protorhus longifolia augments insulin signaling in type 1 diabetic rats

A Lanosteryl triterpene from Protorhus longifolia augments insulin signaling in type 1 diabetic rats

A Lanosteryl Triterpene (RA-3) Exhibits Antihyperuricemic and Nephroprotective Effects in Rats

Pancreatic inflammation induced by hypothyroidism in female rabbits is associated with cholesterol accumulation and a reduced expression of CYP51A1, FXRβ, and PPARβ/δ

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