The inhibitory effects of cannabinoids from cannabis sativa on the enzymes dipeptidyl peptidase-IV, sucrase and maltase as a new therapeutic treatment for type 2 diabetes
- Authors: Viljoen, Zenobia
- Date: 2024-12
- Subjects: Diabetes -- Treatment , Cannabinoids -- Therapeutic use , Medical Marijuana -- therapeutic use
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10948/69516 , vital:77264
- Description: Type 2 diabetes is one of the most prevalent diseases worldwide. The treatments used to manage diabetes often have severe side effects and patients develop resistance to traditional treatment. The project aimed to test if phytocannabinoids from Cannabis sativa inhibited key enzymes involved in glycaemic homeostatic regulation, namely dipeptidyl peptidase 4 (DPP-4), sucrase, and maltase. This study investigated the inhibitory effects of 3 M-128 M cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), and Δ9- tetrahydrocannabinol (THC). CD spectroscopy was used to investigate the changes in the secondary structure of DPP-4 with interacting inhibitors. The effect of 1.25, 2.5, and 5 mg/kg rat THC cannabis extract on the activity of DPP-4 in blood plasma and rat pancreatic tissue of the diabetic rat model and obese rat model. The effect of 1.25, 2.5, and 5 mg/kg rat THC cannabis extract on glucagon concentration in the blood plasma of the diabetic rat model and obese rat model was investigated. The carbohydrate digestive enzymes namely -amylase, -glucosidase and maltase are not inhibited by any of the cannabinoids. CBN had inhibitory effects on sucrase. CBN, CBG, and CBD are mixed inhibitors of DPP-4, thus they can inhibit DPP-4 competitively and uncompetitively depending on the concentration of the cannabinoid. THC was shown in kinetic and rat model studies to be a very weak inhibitor of DPP-4. CD spectroscopy showed that sitagliptin (FDA-approved drug and competitive inhibitor) and CBG mimic the denatured structure of DPP-4. CBD, CBN and THC mimic the free (active) form of DPP-4. A reduction in pancreatic DPP-4 activity was observed with 2.5 and 5 mg/kg rat THC (diabetic model). This study showed that diet plays a role in glycaemic dysregulation (obese rat model) and that insulin-resistant rats had four times higher glucagon levels compared to the lean control (diabetic model). 1.25 mg/kg rat THC reduced blood plasma DPP-4 activity and blood plasma glucagon. Cannabis sativa can be a feasible treatment to help manage type 2 diabetes by inhibiting DPP-4, especially medical strains of Cannabis sativa with high concentrations of CBD and CBG. , Thesis (MSc) -- Faculty of Science, School of Biomolecular & Chemical Sciences, 2024
- Full Text:
- Date Issued: 2024-12
- Authors: Viljoen, Zenobia
- Date: 2024-12
- Subjects: Diabetes -- Treatment , Cannabinoids -- Therapeutic use , Medical Marijuana -- therapeutic use
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10948/69516 , vital:77264
- Description: Type 2 diabetes is one of the most prevalent diseases worldwide. The treatments used to manage diabetes often have severe side effects and patients develop resistance to traditional treatment. The project aimed to test if phytocannabinoids from Cannabis sativa inhibited key enzymes involved in glycaemic homeostatic regulation, namely dipeptidyl peptidase 4 (DPP-4), sucrase, and maltase. This study investigated the inhibitory effects of 3 M-128 M cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), and Δ9- tetrahydrocannabinol (THC). CD spectroscopy was used to investigate the changes in the secondary structure of DPP-4 with interacting inhibitors. The effect of 1.25, 2.5, and 5 mg/kg rat THC cannabis extract on the activity of DPP-4 in blood plasma and rat pancreatic tissue of the diabetic rat model and obese rat model. The effect of 1.25, 2.5, and 5 mg/kg rat THC cannabis extract on glucagon concentration in the blood plasma of the diabetic rat model and obese rat model was investigated. The carbohydrate digestive enzymes namely -amylase, -glucosidase and maltase are not inhibited by any of the cannabinoids. CBN had inhibitory effects on sucrase. CBN, CBG, and CBD are mixed inhibitors of DPP-4, thus they can inhibit DPP-4 competitively and uncompetitively depending on the concentration of the cannabinoid. THC was shown in kinetic and rat model studies to be a very weak inhibitor of DPP-4. CD spectroscopy showed that sitagliptin (FDA-approved drug and competitive inhibitor) and CBG mimic the denatured structure of DPP-4. CBD, CBN and THC mimic the free (active) form of DPP-4. A reduction in pancreatic DPP-4 activity was observed with 2.5 and 5 mg/kg rat THC (diabetic model). This study showed that diet plays a role in glycaemic dysregulation (obese rat model) and that insulin-resistant rats had four times higher glucagon levels compared to the lean control (diabetic model). 1.25 mg/kg rat THC reduced blood plasma DPP-4 activity and blood plasma glucagon. Cannabis sativa can be a feasible treatment to help manage type 2 diabetes by inhibiting DPP-4, especially medical strains of Cannabis sativa with high concentrations of CBD and CBG. , Thesis (MSc) -- Faculty of Science, School of Biomolecular & Chemical Sciences, 2024
- Full Text:
- Date Issued: 2024-12
Inhibitory effects of selected cannabinoids against dipeptidyl peptidase IV, an enzyme linked to type 2 diabetes
- Mkabayi, Lithalethu, Viljoen, Zenobia, Krause, Rui W M, Lobb, Kevin A, Pletschke, Brett I, Frost, Carminita L
- Authors: Mkabayi, Lithalethu , Viljoen, Zenobia , Krause, Rui W M , Lobb, Kevin A , Pletschke, Brett I , Frost, Carminita L
- Date: 2024
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452760 , vital:75168 , xlink:href="https://doi.org/10.1016/j.heliyon.2023.e23289"
- Description: Ethnopharmacological relevance: In recent times the decriminalisation of cannabis globally has increased its use as an alternative medication. Where it has been used in modern medicinal practises since the 1800s, there is limited scientific investigation to understand the biological activities of this plant. Aim of the study: Dipeptidyl peptidase IV (DPP-IV) plays a key role in regulating glucose homeostasis, and inhibition of this enzyme has been used as a therapeutic approach to treat type 2 diabetes. However, some of the synthetic inhibitors for this enzyme available on the market may cause undesirable side effects. Therefore, it is important to identify new inhibitors of DPP-IV and to understand their interaction with this enzyme.
- Full Text:
- Date Issued: 2024
- Authors: Mkabayi, Lithalethu , Viljoen, Zenobia , Krause, Rui W M , Lobb, Kevin A , Pletschke, Brett I , Frost, Carminita L
- Date: 2024
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452760 , vital:75168 , xlink:href="https://doi.org/10.1016/j.heliyon.2023.e23289"
- Description: Ethnopharmacological relevance: In recent times the decriminalisation of cannabis globally has increased its use as an alternative medication. Where it has been used in modern medicinal practises since the 1800s, there is limited scientific investigation to understand the biological activities of this plant. Aim of the study: Dipeptidyl peptidase IV (DPP-IV) plays a key role in regulating glucose homeostasis, and inhibition of this enzyme has been used as a therapeutic approach to treat type 2 diabetes. However, some of the synthetic inhibitors for this enzyme available on the market may cause undesirable side effects. Therefore, it is important to identify new inhibitors of DPP-IV and to understand their interaction with this enzyme.
- Full Text:
- Date Issued: 2024
Inhibiting human dipeptidyl peptidase IV using cannabinoids and Leonotis leonurus extracts as a potential therapy for the management of diabetes
- Mkabayi, Lithalethu, Viljoen, Zenobia, Lobb, Kevin A, Pletschke, Brett I, Frost, Carminita L
- Authors: Mkabayi, Lithalethu , Viljoen, Zenobia , Lobb, Kevin A , Pletschke, Brett I , Frost, Carminita L
- Date: 2023
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452745 , vital:75167 , xlink:href="https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0043-1773924"
- Description: Diabetes is a chronic metabolic disorder that has been shown to affect a growing number of people worldwide. Controlling blood glucose levels is one of the possible strategies to treat type 2 diabetes mellitus (T2DM). It has been established that the inhibition of dipeptidyl peptidase IV (DPP-IV) prolongs the activity of incretin hormones, which serve as key stimulators of insulin secretion and regulation of blood glucose levels. Although several synthetic DPP-IV inhibitors are available, there is still a need for naturally sourced inhibitors that have fewer to no undesirable side effects. In this study, cannabinoids and Leonotis leonurus aqueous extracts were evaluated for their inhibitory effects against recombinant human DPP-IV. Their potential inhibition mechanism was explored using in vitro and in silico approaches. All tested cannabinoids and L. leonurus aqueous extracts showed significant inhibitory activity against DPP-IV. Phytochemical analysis of L. leonurus extract indicated the presence of diterpenoids and alkaloids, which might contribute to the inhibitory activity. In molecular docking studies, among different constituents known in L. leonurus, luteolin and marrubiin showed binding energy of -7.2 kcal/mol and cannabinoids (cannabidiol, cannabigerol, cannabinol and Δ9-tetrahydrocannabinol) showed binding energies ranging from -6.5 to -8.2 kcal/mol. Molecular dynamics revealed that all tested compounds formed stable complexes with the enzyme during 100 ns simulation, indicating that they are good ligands. This study provided preliminary evidence for the potential application of the selected cannabinoids and L. leonurus in maintaining glucose homeostasis, suggesting that they could be suitable therapeutic candidates for managing T2DM.
- Full Text:
- Date Issued: 2023
- Authors: Mkabayi, Lithalethu , Viljoen, Zenobia , Lobb, Kevin A , Pletschke, Brett I , Frost, Carminita L
- Date: 2023
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/452745 , vital:75167 , xlink:href="https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0043-1773924"
- Description: Diabetes is a chronic metabolic disorder that has been shown to affect a growing number of people worldwide. Controlling blood glucose levels is one of the possible strategies to treat type 2 diabetes mellitus (T2DM). It has been established that the inhibition of dipeptidyl peptidase IV (DPP-IV) prolongs the activity of incretin hormones, which serve as key stimulators of insulin secretion and regulation of blood glucose levels. Although several synthetic DPP-IV inhibitors are available, there is still a need for naturally sourced inhibitors that have fewer to no undesirable side effects. In this study, cannabinoids and Leonotis leonurus aqueous extracts were evaluated for their inhibitory effects against recombinant human DPP-IV. Their potential inhibition mechanism was explored using in vitro and in silico approaches. All tested cannabinoids and L. leonurus aqueous extracts showed significant inhibitory activity against DPP-IV. Phytochemical analysis of L. leonurus extract indicated the presence of diterpenoids and alkaloids, which might contribute to the inhibitory activity. In molecular docking studies, among different constituents known in L. leonurus, luteolin and marrubiin showed binding energy of -7.2 kcal/mol and cannabinoids (cannabidiol, cannabigerol, cannabinol and Δ9-tetrahydrocannabinol) showed binding energies ranging from -6.5 to -8.2 kcal/mol. Molecular dynamics revealed that all tested compounds formed stable complexes with the enzyme during 100 ns simulation, indicating that they are good ligands. This study provided preliminary evidence for the potential application of the selected cannabinoids and L. leonurus in maintaining glucose homeostasis, suggesting that they could be suitable therapeutic candidates for managing T2DM.
- Full Text:
- Date Issued: 2023
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