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:
- 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:
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:
- 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:
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