ORCID Profile
0000-0003-4192-7219
Current Organisation
University of Adelaide
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Publisher: Elsevier BV
Date: 02-2021
Publisher: Bentham Science Publishers Ltd.
Date: 04-2021
DOI: 10.2174/1570159X18666200720172624
Abstract: In the last few years research into Cannabis and its constituent phytocannabinoids has burgeoned, particularly in the potential application of novel cannabis phytochemicals for the treatment of erse illnesses related to neurodegeneration and dementia, including Alzheimer’s (AD), Parkinson’s (PD) and Huntington’s disease (HD). To date, these neurological diseases have mostly relied on symptomatological management. However, with an aging population globally, the search for more efficient and disease-modifying treatments that could delay or mitigate disease progression is imperative. In this context, this review aims to present state of the art in the research with cannabinoids and novel cannabinoid-based drug candidates that have been emerged as novel promising alternatives for drug development and innovation in the therapeutics of a number of diseases, especially those related to CNS-disturbance and impairment.
Publisher: Elsevier BV
Date: 11-2019
DOI: 10.1016/J.BCP.2019.08.011
Abstract: Flavonoids form a erse class of naturally occurring polyphenols ascribed various biological activities, including inhibition of amyloid β (Aβ) fibrillisation and neurotoxicity of relevance to Alzheimer's disease. Cannabis contains a unique subset of prenylated flavonoids, the cannflavins. While selected conventional flavonoids have demonstrated anti-amyloid and neuroprotective potential, any neuroprotective bioactivity of prenylated flavonoids has not been determined. We evaluated the in vitro neuroprotective and anti-aggregative properties of the novel geranylated cannabis-derived flavonoid, cannflavin A against Aβ Neuronal viability were assessed in PC12 cells biochemically using the MTT assay in the presence of each flavonoid (1-200 µM) for 48 h. Sub-toxic threshold test concentrations of each flavonoid were then applied to cells, alone or with concomitant incubation with the lipid peroxidant tert-butyl hyrdroperoxide (t-bhp) or amyloid β (Aβ Cannflavin A demonstrated intrinsic hormetic effects on cell viability, increasing viability by 40% from 1 to 10 µM but displaying neurotoxicity at higher (>10-100 µM) concentrations. Neither mimulone nor diplacone exhibited such a biphasic effect, instead showing only concentration-dependent neurotoxicity, with diplacone the more potent (from >1 µM). However at the lower concentrations (<10 µM), cannflavin A increased cell viability by up to 40%, while 10 µM cannflavin A inhibited the neurotoxicity elicited by Aβ These findings highlight a concentration-dependent hormetic and neuroprotective role of cannflavin A against Aβ-mediated neurotoxicity, associated with an inhibition of Aβ fibrillisation. The efficacy of the cannabis flavone may itself direct further lead development targeting neurodegeneration in Alzheimer's disease. However, the geranylated flavonoids generally displayed a comparatively potent neurotoxicity not observed with many conventional flavonoids in vitro.
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2FO02458F
Abstract: The chemotherapeutic drug irinotecan and its active metabolite SN-38 have been linked to the development of off-target gastrointestinal toxicity and inflammation, termed gastrointestinal mucositis (GIM). Flavonoids possess antioxidant and anti-inflammatory effects in models of gastrointestinal inflammation however, few studies have investigated their potential in ameliorating chemotherapy-induced GIM. Here, we characterised the intestinal epithelial barrier-protective and antioxidant capacity of the novel flavonoids 2',3',4'-trihydroxyflavone (2-D08) and transilitin in comparison with flavones myricetin and quercetin
Publisher: Wiley
Date: 25-09-2023
DOI: 10.1111/BCPT.13943
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0FO01438A
Abstract: Ecklonia radiata extract and phlorotannin fraction containing predominantly eckol-type phlorotannins inhibited the cytotoxicity of Aβ 1–42 in neuronal PC-12 cells and evoked a reduction in the density of Aβ 1–42 aggregates.
Publisher: Elsevier BV
Date: 09-2020
Publisher: MDPI AG
Date: 19-05-2019
DOI: 10.3390/MOLECULES24101926
Abstract: White tea (WT) is one of six tea types originally derived from Fujian Province, China. White tea is known for its health-promoting properties. However, the neuroprotective and anti-aggregatory properties of WT against the hallmark toxic Alzheimer’s protein, Aβ have not been investigated. In this study, WT, green tea (GT), oolong tea (OT) and black tea (BT) were manufactured using tea leaves from the cultivar Camellia sinensis (Jin Guanyin). The protective effects of these tea extracts were then studied under oxidative stress conditions via t-bhp and H2O2 exposure, in addition to Aβ treatment using a PC-12 cell model. Each tea type failed to rescue PC-12 cells from either t-bhp or H2O2-mediated toxicity, however each extract exerted significant protection against Aβ-evoked neurotoxicity. Results of the Thioflavin T Kinetic (ThT) and TEM assay showed that Aβ aggregate formation was inhibited by each tea type. Additionally, TEM also supported the different anti-aggregatory effect of WT by modifying Aβ into an amorphous and punctate aggregate morphology. Higher accumulated precedent or potential neuroprotective compounds in WT, including ECG’’3Me, 8-C-ascorbyl-EGCG, GABA and Gln, in addition to flavonol or flavone glycosides detected by using UPLC-QTOF-MS and UPLC-QqQ-MS, may contribute to a favourable anti-aggregative and neuroprotective effect of WT against Aβ.
Publisher: Elsevier BV
Date: 12-2022
DOI: 10.1016/J.PHYMED.2022.154485
Abstract: Neurodegenerative diseases and dementia pose a global health challenge in an aging population, exemplified by the increasing incidence and prevalence of its most common form, Alzheimer's disease. Although several approved treatments exist for Alzheimer's disease, they only afford transient symptomatic improvements and are not considered disease-modifying. The psychoactive properties of Cannabis sativa L. have been recognized for thousands of years and now with burgeoning access to medicinal formulations globally, research has turned to re-evaluate cannabis and its myriad phytochemicals as a potential treatment and adjunctive agent for neurodegenerative diseases. This review evaluated the neuroprotective potential of C. sativa's active constituents for potential therapeutic use in dementia and Alzheimer's disease, based on published studies demonstrating efficacy in experimental preclinical settings associated with neurodegeneration. Relevant information on the neuroprotective potential of the C. sativa's phytoconstituents in preclinical studies (in vitro, in vivo) were included. The collated information on C. sativa's component bioactivity was organized for therapeutic applications against neurodegenerative diseases. The therapeutic use of C. sativa related to Alzheimer's disease relative to known phytocannabinoids and other phytochemical constituents were derived from online databases, including PubMed, Elsevier, The Plant List (TPL, www.theplantlist.org), Science Direct, as well as relevant information on the known pharmacological actions of the listed phytochemicals. Numerous C. sativa -prevalent phytochemicals were evidenced in the body of literature as having efficacy in the treatment of neurodegenerative conditions exemplified by Alzheimer's disease. Several phytocannabinoids, terpenes and select flavonoids demonstrated neuroprotection through a myriad of cellular and molecular pathways, including cannabinoid receptor-mediated, antioxidant and direct anti-aggregatory actions against the pathological toxic hallmark protein in Alzheimer's disease, amyloid β. These findings provide strong evidence for a role of cannabis constituents, in idually or in combination, as potential neuroprotectants timely to the emergent use of medicinal cannabis as a novel treatment for neurodegenerative diseases. Future randomized and controlled clinical studies are required to substantiate the bioactivities of phytocannabinoids and terpenes and their likely synergies.
Publisher: CSIRO Publishing
Date: 18-09-2020
DOI: 10.1071/CH20183
Abstract: With the advent of medical cannabis usage globally, there has been a renewed interest in exploring the chemical ersity of this unique plant. Cannabis produces hundreds of unique phytocannabinoids, which not only have erse chemical structures but also a range of cellular and molecular actions, interesting pharmacological properties, and biological actions. In addition, it produces other flavonoids, stilbenoids, and terpenes that have been variably described as conferring additional or so-called entourage effects to whole-plant extracts when used in therapeutic settings. This review explores this phytochemical ersity in relation to specific bioactivity ascribed to phytocannabinoids as neuroprotective agents. It outlines emergent evidence for the potential for selected phytocannabinoids and other cannabis phytochemicals to mitigate factors such as inflammation and oxidative stress as drivers of neurotoxicity, in addition to focusing on specific interactions with pathological misfolding proteins, such as amyloid β, associated with major forms of neurodegenerative diseases such as Alzheimer’s disease.
Publisher: American Chemical Society (ACS)
Date: 13-11-2020
Start Date: 2018
End Date: 2018
Funder: Japan Society for the Promotion of Science
View Funded ActivityStart Date: 2013
End Date: 2015
Funder: University of Adelaide
View Funded Activity