The present study aimed to investigate the rationale and efficacy of testing endogenous substances widely used as dietary supplement such as citicoline,coenzyme Q10(CoQ10)and a fixed combination of them in countering ...The present study aimed to investigate the rationale and efficacy of testing endogenous substances widely used as dietary supplement such as citicoline,coenzyme Q10(CoQ10)and a fixed combination of them in countering the oxidative stress and neurotoxicity occurring in neurological diseases.Rat CTX-TNA2 astrocytes,which have considerable antioxidant potential and could represent a key target for neurotherapies were selected as in vitro model to conduct the experiments.The efficacy of citicoline and coenzyme Q10(1 nM-10μM),with their fixed combination,were assayed in rat astrocytes either in basal condition or after challenging the cells with hydrogen peroxide in order to evaluate the biocompatibility of treatments.The gene expression of B-Cell Lymphoma protein 2(BCL-2),BCL-2 Associated X(BAX),Superoxide dismutase 2(SOD2),Cardiolipin Synthase 1(CRLS1),interleukin-6(IL-6),tumor necrosis factorα(TNFα),and nuclear factor kappa-light-chain-enhancer of activated B cells(NFkB)involved in neurodegenerative diseases and neuroinflammation were investigated in CTX-TNA2 cells.Furthermore,in the same condition,Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)was carried out to assess apoptosis in astrocytes.Neither citicoline,nor coenzyme Q10 significantly altered astrocytes cell viability;thus,suggesting the biocompatibility of single ingredients and fixed combination in the concentration range considered for the study.Moreover,each compound tested alone or in combination were effective in inhibiting the hydrogen peroxide-induced gene expression of BAX,and SOD2,in inducing the gene expression of BCL-2 and CRLS1 and in reducing apoptosis.The blunting effects induced by the above-mentioned treatments on hydrogen-peroxide induced apoptosis was also confirmed by TUNEL assay that demonstrated the capability of citicoline,CoQ10,and their combination to reduce the ratio TUNEL positive nuclei/total nuclei,a reliable marker of apoptosis.Additionally,citicoline,CoQ10,and their association were effective in inhibiting the hydrogen peroxide-induced NFkB,TNFα,and IL-6 gene.In parallel,there was an in-hibition of both TNFαand IL-6 gene expression in basal condition.The co-administration of citicoline/coenzyme Q10 was overall more effective than individual ingredients.The present findings support the beneficial and synergistic effects of citicoline and coenzyme Q10 in fixed combination in reducing oxidation,and in stimulating neuroprotection in rat CTX-TNA2 astrocytes.展开更多
The study focused on investigating the phytochemical composition and bio-pharmacological properties of a water extract obtained from industrial hemp by-products,after trimming female inflorescences of Cannabis sativa ...The study focused on investigating the phytochemical composition and bio-pharmacological properties of a water extract obtained from industrial hemp by-products,after trimming female inflorescences of Cannabis sativa L.,cultivar Kompolti.The extract was found to be rich in phenolic compounds,particularly gallic acid,catechin,coumaric acid,ferulic acid,and benzoic acid.It also contained significant amounts of cannabidiolic acid and cannabigerolic acid as the main terpenophenols.To assess the biological potential of the extract,various ecotoxicological assays were conducted.The extract did not show significant phytotoxic effects on seedling germination in the allelopathic assay.In the brine shrimp(Artemia salina)lethality test,the LC50 value was 1.726 mg/mL,and in the Daphnia magna test,the extract showed no cardiotoxicity effects at the same concentration;thus,confirming its biocompatibility with these eukaryotic organisms.Additionally,the extract did not induce cytotoxicity in the murine C2C12 cell line till to the concentration of 1000μg/mL.In isolated mouse prostate specimens,the extract(10-1000μg/mL)also prevented LPS-induced gene expression of pro-inflammatory cytokines,namely tumor necrosis factor(TNF)α,interleukin(IL)-6,and IL-1β.Furthermore,the extract exhibited inhibitory effects on the growth of pathogenic bacterial,fungal,and dermatophyte species commonly associated with prostatitis.These results suggest that the residual powder from female inflorescence trimming can be considered an innovative plant material from the industrial hemp supply chain that deserves to be valorised in terms of recycling and upcycling;thus,reducing the environmental impact of the by-products and also opening the way for innovative health-promoting agents.展开更多
文摘The present study aimed to investigate the rationale and efficacy of testing endogenous substances widely used as dietary supplement such as citicoline,coenzyme Q10(CoQ10)and a fixed combination of them in countering the oxidative stress and neurotoxicity occurring in neurological diseases.Rat CTX-TNA2 astrocytes,which have considerable antioxidant potential and could represent a key target for neurotherapies were selected as in vitro model to conduct the experiments.The efficacy of citicoline and coenzyme Q10(1 nM-10μM),with their fixed combination,were assayed in rat astrocytes either in basal condition or after challenging the cells with hydrogen peroxide in order to evaluate the biocompatibility of treatments.The gene expression of B-Cell Lymphoma protein 2(BCL-2),BCL-2 Associated X(BAX),Superoxide dismutase 2(SOD2),Cardiolipin Synthase 1(CRLS1),interleukin-6(IL-6),tumor necrosis factorα(TNFα),and nuclear factor kappa-light-chain-enhancer of activated B cells(NFkB)involved in neurodegenerative diseases and neuroinflammation were investigated in CTX-TNA2 cells.Furthermore,in the same condition,Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)was carried out to assess apoptosis in astrocytes.Neither citicoline,nor coenzyme Q10 significantly altered astrocytes cell viability;thus,suggesting the biocompatibility of single ingredients and fixed combination in the concentration range considered for the study.Moreover,each compound tested alone or in combination were effective in inhibiting the hydrogen peroxide-induced gene expression of BAX,and SOD2,in inducing the gene expression of BCL-2 and CRLS1 and in reducing apoptosis.The blunting effects induced by the above-mentioned treatments on hydrogen-peroxide induced apoptosis was also confirmed by TUNEL assay that demonstrated the capability of citicoline,CoQ10,and their combination to reduce the ratio TUNEL positive nuclei/total nuclei,a reliable marker of apoptosis.Additionally,citicoline,CoQ10,and their association were effective in inhibiting the hydrogen peroxide-induced NFkB,TNFα,and IL-6 gene.In parallel,there was an in-hibition of both TNFαand IL-6 gene expression in basal condition.The co-administration of citicoline/coenzyme Q10 was overall more effective than individual ingredients.The present findings support the beneficial and synergistic effects of citicoline and coenzyme Q10 in fixed combination in reducing oxidation,and in stimulating neuroprotection in rat CTX-TNA2 astrocytes.
基金the joint project(2020-2023)between Department of Pharmacy of“G.d’Annunzio”University and Veridia S.r.l.aimed to the valorization of industrial hemp cultivation in the Middle Italy,Abruzzo Region.Project coordinators are Giustino Orlando,Luigi Menghini,and Claudio Ferrantefunded the industrial PhD project of Dr.Alessandra Acquaviva entitled:“Cannabis and circular economy:enhancing an agricultural supply chain with a high social impact,for the development of agroindustry through botanical innovations and related applications in the nutraceutical,pharmacological,cosmetic/cosmeceutical and health sectors in general”.Academic tutors are Giustino Orlando and Claudio Ferrantesupported by the Cristalfarma S.r.l.that funded the PhD project of Dr.Simonetta Cristina Di Simone entitled“From the Botanical Garden“Giardino dei Semplici”to modern rational phytotherapy:Enhancement of biodiversity and study of plant extracts in complex mixtures for innovative phytotherapeutic applications”.Academic tutors are Luigi Menghini and Claudio Ferrante.
文摘The study focused on investigating the phytochemical composition and bio-pharmacological properties of a water extract obtained from industrial hemp by-products,after trimming female inflorescences of Cannabis sativa L.,cultivar Kompolti.The extract was found to be rich in phenolic compounds,particularly gallic acid,catechin,coumaric acid,ferulic acid,and benzoic acid.It also contained significant amounts of cannabidiolic acid and cannabigerolic acid as the main terpenophenols.To assess the biological potential of the extract,various ecotoxicological assays were conducted.The extract did not show significant phytotoxic effects on seedling germination in the allelopathic assay.In the brine shrimp(Artemia salina)lethality test,the LC50 value was 1.726 mg/mL,and in the Daphnia magna test,the extract showed no cardiotoxicity effects at the same concentration;thus,confirming its biocompatibility with these eukaryotic organisms.Additionally,the extract did not induce cytotoxicity in the murine C2C12 cell line till to the concentration of 1000μg/mL.In isolated mouse prostate specimens,the extract(10-1000μg/mL)also prevented LPS-induced gene expression of pro-inflammatory cytokines,namely tumor necrosis factor(TNF)α,interleukin(IL)-6,and IL-1β.Furthermore,the extract exhibited inhibitory effects on the growth of pathogenic bacterial,fungal,and dermatophyte species commonly associated with prostatitis.These results suggest that the residual powder from female inflorescence trimming can be considered an innovative plant material from the industrial hemp supply chain that deserves to be valorised in terms of recycling and upcycling;thus,reducing the environmental impact of the by-products and also opening the way for innovative health-promoting agents.
