2019_Effect of Phenolic Acids in Pomegranate (Punica Granatum) Extract as Non-Opioid Substitution Therapy for Morphine Dependent Treatment
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| collectionurl | https://intelek.unisza.edu.my/intelek/pages/search.php?search=!collection3 |
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| country | Malaysia |
| date | 2019-10-02 |
| format | General Document |
| id | 15823 |
| institution | UniSZA |
| internalnotes | Sila masukkan subject wajib Dissertations, Academic. Terima kasih... |
| originalfilename | EFFECT OF PHENOLIC ACIDS IN POMEGRANATE (PUNICA GRANATUM) EXTRACT AS NON-OPIOID SUBSTITUTION THERAPY FOR MORPHINE DEPENDENT TREATMENT (MASTER_2019).pdf |
| person | Mimie Noratiqah Jumli |
| recordtype | oai_dc |
| resourceurl | https://intelek.unisza.edu.my/intelek/pages/view.php?ref=15823 |
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| spelling | 15823 https://intelek.unisza.edu.my/intelek/pages/view.php?ref=15823 https://intelek.unisza.edu.my/intelek/pages/search.php?search=!collection3 General Document Malaysia Library Staff (Top Management) Library Staff (Management) Library Staff (Support) Terengganu Faculty of Health Sciences English application/pdf 1.5 Server storage Scanned document Universiti Sultan Zainal Abidin UniSZA Private Access UNIVERSITI SULTAN ZAINAL ABIDIN SAMBox 2.3.4; modified using iTextSharp™ 5.5.10 ©2000-2016 iText Group NV (AGPL-version) Copyright©PWB2025 199 2019-10-02 EFFECT OF PHENOLIC ACIDS IN POMEGRANATE (PUNICA GRANATUM) EXTRACT AS NON-OPIOID SUBSTITUTION THERAPY FOR MORPHINE DEPENDENT TREATMENT (MASTER_2019).pdf 2019_Effect of Phenolic Acids in Pomegranate (Punica Granatum) Extract as Non-Opioid Substitution Therapy for Morphine Dependent Treatment Mimie Noratiqah Jumli Phenolic acids—Pharmacological aspects Overconsumption of morphine can cause withdrawal syndromes after discontinuation and decreases its effectiveness. Methadone is commonly used opioid substitution therapy to overcome morphine dependent opioid withdrawal syndrome. However, the methadone detoxification is slow and frequently accompanied by withdrawal syndromes. Pomegranates contain abundant phenolic compounds, which potentially improve cognitive function for memory impairment in managing the withdrawal syndrome. The current study aimed to identify phenolic acid compounds in pomegranate (PPA), to analyse the cytotoxicity of dose response of PPA extract and morphine sulphate toward Human Glioblastoma multiforme Cancer Cell U87 and to correlate the levels of Mµ-opioid Receptor (MOR) and Cyclic Adenosine Monophosphate (cAMP) protein, to evaluate the effect of PPA extract toward the memory impairment of morphine induced Sprague-Dawley rats and correlate the level of Brain Derivative Neutrophic Factor (BDNF) and cAMP Response Element Binding (CREB) from serum blood of rats. High-Performance Liquid Chromatography (HPLC) was used to quantify the composition of three phenolic acids in pomegranate extract by using three different extraction methods with two different solvents. The HPLC isocratic method was developed for the validation by using external standard compounds [Ellagic Acid (EA), Ferulic Acid (FA) and Gallic Acid (GA)], while quantification of the compounds in the sample was compared with the external standard data. In-vitro was focused on acute morphine induced group and chronic morphine induced; each of acute and chronic group induced consist of five subgroups [Normal (NL) group, morphine (ME) group, morphine treated with methadone (MM) group, morphine treated with naloxone (MN) group and morphine treated with pomegranate phenolic acid (MPPA) group]. In-vitro study was done by 3-[4, 5- dimethylthiazol-2-yl]-2-5-diphenyltetrazolium bromide (MTT) assay to determine the optimum safe dose of morphine and PPA extract on the cells. The level of MOR and cAMP was determined by using assays. Meanwhile, In-vivo study was focued on acute morphine induced group and chronic morphine induced; each of morphine group induced consist of four subgroups [Normal (NL) group, morphine (ME) group, morphine treated with methadone (MM) group, and morphine treated with pomegranate phenolic acid (MPPA) group]. In-vivo study was focus to determine the memory impairment by using Morris Water Maze test (MWM). Blood serum of the rats was used to analyse the CREB and BDNF protein levels. Results showed that blended water extraction method contain a higher level of EA (0.85 ± 0.06 mg/100 g e.p), FA (0.95 ± 0.04 mg/100 g e.p) and GA (57.9 3± 2.66 mg/100 g e.p) compared to other methods applied. The cytotoxic activity In-vitro study showed that morphine and PPA extract obtained the IC50 at 1.60 µg/mL and 0.39 mg/mL, respectively. Optimum concentration at 0.625 ug/mL and 0.125 mg/mL of morphine and PPA extract, respectively was chosen based on the regulation of MOR and cAMP levels. The treatment of MPPA group showed a significant decline (p<0.05) in cAMP level as compared to the MM group. Data from the in-vivo study showed that MPPA group had significantly improved 44% memory impairment by reducing the swimming distance and time latency compared to the ME group and showed 25% improved memory impairment by comparing with MM group. The blood serum of rats showed that MPPA group had significant reduction (p<0.05) in CREB level and significant increased (p<0.05) in BDNF level compared to the ME group. Besides, the CREB level showed good correlation with the BDNF proteins level. Therefore, the current study found that phenolic acids in the pomegranate extract have the potential to be used as a non-substitution therapy for morphine-dependent treatment. Dissertations, Academic Sila masukkan subject wajib Dissertations, Academic. Terima kasih... Phenolic Acids And Opioid Withdrawal Pomegranate Extract As An Addiction Therapy Non-Opioid Alternatives For Morphine Dependence Thesis |
| spellingShingle | 2019_Effect of Phenolic Acids in Pomegranate (Punica Granatum) Extract as Non-Opioid Substitution Therapy for Morphine Dependent Treatment |
| state | Terengganu |
| subject | Phenolic acids—Pharmacological aspects Dissertations, Academic |
| summary | Overconsumption of morphine can cause withdrawal syndromes after discontinuation and decreases its effectiveness. Methadone is commonly used opioid substitution therapy to overcome morphine dependent opioid withdrawal syndrome. However, the methadone detoxification is slow and frequently accompanied by withdrawal syndromes. Pomegranates contain abundant phenolic compounds, which potentially improve cognitive function for memory impairment in managing the withdrawal syndrome. The current study aimed to identify phenolic acid compounds in pomegranate (PPA), to analyse the cytotoxicity of dose response of PPA extract and morphine sulphate toward Human Glioblastoma multiforme Cancer Cell U87 and to correlate the levels of Mµ-opioid Receptor (MOR) and Cyclic Adenosine Monophosphate (cAMP) protein, to evaluate the effect of PPA extract toward the memory impairment of morphine induced Sprague-Dawley rats and correlate the level of Brain Derivative Neutrophic Factor (BDNF) and cAMP Response Element Binding (CREB) from serum blood of rats. High-Performance Liquid Chromatography (HPLC) was used to quantify the composition of three phenolic acids in pomegranate extract by using three different extraction methods with two different solvents. The HPLC isocratic method was developed for the validation by using external standard compounds [Ellagic Acid (EA), Ferulic Acid (FA) and Gallic Acid (GA)], while quantification of the compounds in the sample was compared with the external standard data. In-vitro was focused on acute morphine induced group and chronic morphine induced; each of acute and chronic group induced consist of five subgroups [Normal (NL) group, morphine (ME) group, morphine treated with methadone (MM) group, morphine treated with naloxone (MN) group and morphine treated with pomegranate phenolic acid (MPPA) group]. In-vitro study was done by 3-[4, 5- dimethylthiazol-2-yl]-2-5-diphenyltetrazolium bromide (MTT) assay to determine the optimum safe dose of morphine and PPA extract on the cells. The level of MOR and cAMP was determined by using assays. Meanwhile, In-vivo study was focued on acute morphine induced group and chronic morphine induced; each of morphine group induced consist of four subgroups [Normal (NL) group, morphine (ME) group, morphine treated with methadone (MM) group, and morphine treated with pomegranate phenolic acid (MPPA) group]. In-vivo study was focus to determine the memory impairment by using Morris Water Maze test (MWM). Blood serum of the rats was used to analyse the CREB and BDNF protein levels. Results showed that blended water extraction method contain a higher level of EA (0.85 ± 0.06 mg/100 g e.p), FA (0.95 ± 0.04 mg/100 g e.p) and GA (57.9 3± 2.66 mg/100 g e.p) compared to other methods applied. The cytotoxic activity In-vitro study showed that morphine and PPA extract obtained the IC50 at 1.60 µg/mL and 0.39 mg/mL, respectively. Optimum concentration at 0.625 ug/mL and 0.125 mg/mL of morphine and PPA extract, respectively was chosen based on the regulation of MOR and cAMP levels. The treatment of MPPA group showed a significant decline (p<0.05) in cAMP level as compared to the MM group. Data from the in-vivo study showed that MPPA group had significantly improved 44% memory impairment by reducing the swimming distance and time latency compared to the ME group and showed 25% improved memory impairment by comparing with MM group. The blood serum of rats showed that MPPA group had significant reduction (p<0.05) in CREB level and significant increased (p<0.05) in BDNF level compared to the ME group. Besides, the CREB level showed good correlation with the BDNF proteins level. Therefore, the current study found that phenolic acids in the pomegranate extract have the potential to be used as a non-substitution therapy for morphine-dependent treatment. |
| title | 2019_Effect of Phenolic Acids in Pomegranate (Punica Granatum) Extract as Non-Opioid Substitution Therapy for Morphine Dependent Treatment |
| title_full | 2019_Effect of Phenolic Acids in Pomegranate (Punica Granatum) Extract as Non-Opioid Substitution Therapy for Morphine Dependent Treatment |
| title_fullStr | 2019_Effect of Phenolic Acids in Pomegranate (Punica Granatum) Extract as Non-Opioid Substitution Therapy for Morphine Dependent Treatment |
| title_full_unstemmed | 2019_Effect of Phenolic Acids in Pomegranate (Punica Granatum) Extract as Non-Opioid Substitution Therapy for Morphine Dependent Treatment |
| title_short | 2019_Effect of Phenolic Acids in Pomegranate (Punica Granatum) Extract as Non-Opioid Substitution Therapy for Morphine Dependent Treatment |
| title_sort | 2019_effect of phenolic acids in pomegranate (punica granatum) extract as non-opioid substitution therapy for morphine dependent treatment |