Flavonoid and cannabinoid impact on the ocular surface

 Media Kit - Current Opinion in Allergy and Clinical Immunology | Lippincott  Audience Solutions | Wolters Kluwer“Purpose of review: To evaluate the impact of flavonoids and cannabinoids as anti-inflammatory and antiallergic treatments on the anterior surface of the eye.

Recent findings: Allergic conjunctivitis and dry eye syndrome are common ocular surface diseases that have been treated with traditional pharmacological measures, e.g. corticosteroids, antihistamines. Given the side-effect profiles of these medications and the growing interest in complementary treatment modalities as part of integrative medical interventions, well known flavonoids, such as quercetin and catechin, are under investigation for topical and systemic application methods for relief. As flavonoid derivatives, pycnogenol and epigallocatechin gallate have alleviated dry eye symptoms, including lacrimal gland inflammation, tear secretion, and the stability of the tear film. Research on ocular cannabinoid receptors and response to synthetic cannabinoids are also being considered for therapy of anterior ocular disorders. The expansion of herbal formulations provides a framework for future treatment regimens for ocular surface disorders.

Summary: Flavonoids and cannabinoids show promise as potential complementary treatment for allergic diseases because of their anti-inflammatory and antiallergic properties. Several studies implementing ocular and systemic application of these compounds show potential in becoming adjuvant treatment strategies for improving quality of life while also managing ocular surface disease processes.”

https://pubmed.ncbi.nlm.nih.gov/32796166/

https://journals.lww.com/co-allergy/Abstract/2020/10000/Flavonoid_and_cannabinoid_impact_on_the_ocular.11.aspx

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Novel cannabis flavonoid, cannflavin A displays both a hormetic and neuroprotective profile against amyloid β-mediated neurotoxicity in PC12 cells: comparison with geranylated flavonoids, mimulone and diplacone.

Biochemical Pharmacology

“Flavonoids form a diverse 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 Aβ1-42 and compared it to two similarly geranylated flavonoids, mimulone and diplacone, to compare the bioactive properties of these unique flavonoids more broadly.

RESULTS:

Cannflavin A demonstrated intrinsic hormetic effects on cell viability, increasing viability by 40% from 1-10µM but displaying neurotoxicity at higher (>10-100µM) 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 (<10µM), cannflavin A increased cell viability by up to 40%, while 10µM cannflavin A inhibited the neurotoxicity elicited by Aβ1-42 (0-2µM), reducing Aβ aggregate adherence to PC-12 cells and associated neurite loss. The neuroprotective effects of cannflavin A were associated with a direct inhibition of Aβ1-42 fibril and aggregate density, evidenced by attenuated ThT fluorescence kinetics and microscopic evidence of both altered and diminished density of Aβ aggregate and fibril morphology via electron microscopy.

CONCLUSIONS:

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.”

https://www.ncbi.nlm.nih.gov/pubmed/31437460

https://www.sciencedirect.com/science/article/abs/pii/S0006295219302990?via%3Dihub

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Flavonoid Derivative of Cannabis Demonstrates Therapeutic Potential in Preclinical Models of Metastatic Pancreatic Cancer.

Image result for frontiers oncology“Pancreatic cancer is particularly refractory to modern therapies, with a 5-year survival rate for patients at a dismal 8%.

One of the significant barriers to effective treatment is the immunosuppressive pancreatic tumor microenvironment and development of resistance to treatment. New treatment options to increase both the survival and quality of life of patients are urgently needed.

This study reports on a new non-cannabinoid, non-psychoactive derivative of cannabis, termed FBL-03G, with the potential to treat pancreatic cancer.

In vitro results show major increase in apoptosis and consequential decrease in survival for two pancreatic cancer models- Panc-02 and KPC pancreatic cancer cells treated with varying concentrations of FBL-03G and radiotherapy.

Meanwhile, in vivo results demonstrate therapeutic efficacy in delaying both local and metastatic tumor progression in animal models with pancreatic cancer when using FBL-03G sustainably delivered from smart radiotherapy biomaterials.

Repeated experiments also showed significant (P < 0.0001) increase in survival for animals with pancreatic cancer compared to control cohorts.

The findings demonstrate the potential for this new cannabis derivative in the treatment of both localized and advanced pancreatic cancer, providing impetus for further studies toward clinical translation.”

https://www.ncbi.nlm.nih.gov/pubmed/31396485

“In this study, a flavonoid derivative of cannabis demonstrates significant therapy potential in the treatment of pancreatic cancer, including radio-sensitizing and cancer metastasis treatment potential. The results justify further studies to optimize therapy outcomes toward clinical translation.”

https://www.frontiersin.org/articles/10.3389/fonc.2019.00660/full

“Flavonoids as anticancer agents: structure-activity relationship study.”  https://www.ncbi.nlm.nih.gov/pubmed/12678721

“The antitumor activities of flavonoids.”  https://www.ncbi.nlm.nih.gov/pubmed/16097445

“Anticancer properties of flavonoids: roles in various stages of carcinogenesis.”  https://www.ncbi.nlm.nih.gov/pubmed/21644918

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Chromatographic Analyses, In Vitro Biological Activities, and Cytotoxicity of Cannabis sativa L. Essential Oil: A Multidisciplinary Study.

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“Due to renewed interest in the cultivation and production of Italian Cannabis sativa L., we proposed a multi-methodological approach to explore chemically and biologically both the essential oil and the aromatic water of this plant. We reported the chemical composition in terms of cannabinoid content, volatile component, phenolic and flavonoid pattern, and color characteristics. Then, we demonstrated the ethnopharmacological relevance of this plant cultivated in Italy as a source of antioxidant compounds toward a large panel of enzymes (pancreatic lipase, α-amylase, α-glucosidase, and cholinesterases) and selected clinically relevant, multidrug-sensible, and multidrug-resistant microbial strains (Staphylococcus aureusHelicobacter pyloriCandida, and Malassezia spp.), evaluating the cytotoxic effects against normal and malignant cell lines. Preliminary in vivo cytotoxicity was also performed on Galleria mellonella larvae. The results corroborate the use of this natural product as a rich source of important biologically active molecules with particular emphasis on the role exerted by naringenin, one of the most important secondary metabolites.”

https://www.ncbi.nlm.nih.gov/pubmed/30544765

https://www.mdpi.com/1420-3049/23/12/3266

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Peltatoside Isolated from Annona crassiflora Induces Peripheral Antinociception by Activation of the Cannabinoid System.

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“Peltatoside is a natural compound isolated from leaves of Annona crassiflora Mart., a plant widely used in folk medicine.

This substance is an analogue of quercetin, a flavonoid extensively studied because of its diverse biological activities, including analgesic effects. Besides, a previous study suggested, by computer structure analyses, a possible quercetin-CB1 cannabinoid receptor interaction.

Thus, the aim of this work was to assess the antinociceptive effect of peltatoside and analyze the cannabinoid system involvement in this action.

Our results suggest that this natural substance is capable of inducing analgesia through the activation of peripheral CB1 receptors, involving endocannabinoids in this process.”

http://www.ncbi.nlm.nih.gov/pubmed/27574895

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Anti Proliferative and Pro Apoptotic Effects of Flavonoid Quercetin Are Mediated by CB1 Receptor in Human Colon Cancer Cell Lines.

“Quercetin, the major constituent of flavonoid and widely present in fruits and vegetables, is an attractive compound for cancer prevention due to its beneficial anti proliferative effects, showing a crucial role in the regulation of apoptosis and cell cycle signaling.

In vitro studies have demonstrated that quercetin specifically influences colon cancer cell proliferation.

Our experiments, using human colon adenocarcinoma cells, confirmed the anti proliferative effect of quercetin and gave intriguing new insight in to the knowledge of the mechanisms involved…

These findings open new perspectives for anticancer therapeutic strategies.”

http://www.ncbi.nlm.nih.gov/pubmed/25893829

“Flavonoid glycosides and cannabinoids from the pollen of Cannabis sativa L.”  http://www.ncbi.nlm.nih.gov/pubmed/15688956

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Flavonoid glycosides and cannabinoids from the pollen of Cannabis sativa L.

“Chemical investigation of the pollen grain collected from male plants of Cannabis sativa L. resulted in the isolation for the first time of two flavonol glycosides from the methanol extract, and the identification of 16 cannabinoids in the hexane extract. The two glycosides were identified as kaempferol 3-O-sophoroside and quercetin 3-O-sophoroside by spectroscopic methods including high-field two-dimensional NMR experiments. The characterisation of each cannabinoid was performed by GC-FID and GC-MS analyses and by comparison with both available reference cannabinoids and reported data. The identified cannabinoids were delta9-tetrahydrocannabiorcol, cannabidivarin, cannabicitran, delta9-tetrahydrocannabivarin, cannabicyclol, cannabidiol, cannabichromene, delta9-tetrahydrocannabinol, cannabigerol, cannabinol, dihydrocannabinol, cannabielsoin, 6a, 7, 10a-trihydroxytetrahydrocannabinol, 9, 10-epoxycannabitriol, 10-O-ethylcannabitriol, and 7, 8-dehydro-10-O-ethylcannabitriol.”

http://www.ncbi.nlm.nih.gov/pubmed/15688956

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