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Home > Capability of Bioactive Compounds from Medicinal Plants to Ameliorate the Neuronal Destruction in Animal Model of Parkinson Disease

Capability of Bioactive Compounds from Medicinal Plants to Ameliorate the Neuronal Destruction in Animal Model of Parkinson Disease

Thesis Info

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Author

Muhammad Rashid Ahmed

Program

PhD

Country

Pakistan

Thesis Completing Year

2018

Thesis Completion Status

Completed

Subject

Anatomy

Language

English

Link

http://prr.hec.gov.pk/jspui/bitstream/123456789/11196/1/Muhammad%20Rashid%20Ahmed_Anatomy_2018_Baqai_PRR.pdf

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676725661351

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OBJECTIVE: To study the capability of bioactive compounds to ameliorate the neuronal destruction in animal model of Parkinson disease. MATERIALS AND METHODS:Rotenone was used to produce the Parkinsonism in mammalian model of rats and the bioactive compounds, chrysin, polydatin and CGA were used to ameliorate the neuronal destruction and the resulting effets of Parkinson in this study. A total of hundred male Sprague Dawley albino rats of weight 200 to 250 gm were divided randomly into five groups with twenty animals in each: control, rotenone+chrysin, rotenone+polydatin and rotenone+chlorogenic acid (CGA) group. Rotenone was dissolved in DMSO and migloyl 812 N at ratio of 2:98 respectively and was administered intraperitoneally at a dose of 3 mg/kg, daily for four week to produce the rat model of Parkinson disease. Mortality and weight changes were assessed, various behavioral tests were performed throughout the experiment to assess the neuro behavioral changes. At the end of experiment, animals were sacrificed, brains were fixed by perfusion method and light microscopic sections were prepared using H & E and cresyl violet method. Immunohistochemical sections were also prepared using anti tyrosine hydroxylase antibody, anti α synuclein antibody, anti ubiquitin antibody, to localize the damaged neurons and amelioration done by bioactive compounds. Anti GFAP antibody was used to localize the Astrocytes immunohistochemically. Dopaminergic neurons, α synuclein and ubiquitin aggregations and astrocytes were analysed for anychanges in their morphology and count in substantia nigra and striatum in Parkinsonism and the ameliorating effects of the bioactive compounds used in this study on them. RESULTS:Rotenone-induced Parkinsonism in animals showed a significant loss of body weight and increase in mortality.Parkinson animals showed deteriorating motor behaviour over the period of experiment. Parkinson animals showed a decrease in dopaminergic neurons in nigrostriatal region. TH immunohistochemistry (IHC) showed decreased immunoreactivity and number of TH positive dopaminergic neurons.Ubiquitin and α-synuclein IHC showed accumulation of α-synuclein & ubiquitin within the neuronal cytoplasm. Astrogliosis with increase in number and amoeboid morphology was also seen. Bioactive compounds not only significantly restored the rotenone-induced weight loss but also the behavioural changes. These compounds also showed protective effects in terms of less degeneration of nigrostriatal dopaminergic neurons and diminished immunoreactivity to anti ubiquitin and anti α-synuclein antibodies. These compounds also decreased the activation and number of astrocytes. CONCLUSION:This study concludes that bioactive compounds confer protection in rat model of Parkinson disease. They ameliorated the degeneration of the dopaminergic neurons, accumulation of α-synuclein and ubiquitin in the cytoplasm of neurons and activation & morphological alteration of astrocytes.
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مولانافضل حق رامپوری

مولانا فضل حق رامپوری ؍ مولانا معین الدین اجمیری
افسوس ہے کہ پچھلے دو مہینوں میں ہماری قدیم تعلیم کے خزانہ کے دو انمول موتی کھوگئے، ایک مولانا فضل حق صاحب رامپوری جو مدرسہ عالیہ رامپور میں مدرس اعلیٰ تھے، موصوف نے نصف صدی تک علوم اسلامیہ کی تدریس کا فرض انجام دیا تھا، ۸۱ برس کی عمر میں دار فانی کو الوداع کہا، اور اب ۱۰؍ محرم ۱۳۵۹؁ھ کی دوپہر کو مولانا معین الدین اجمیری نے جن کو سلسلہ خیرآباد کا خاتم کہنا چاہیے وفات پائی، مرحوم مولانا برکات احمد صاحب ٹونکی کے ارشد تلامذہ میں تھے، اور عمر بھر درس و تدریس میں گذار دی، حضرت خواجہ معین الدین چشتی رحمتہ اﷲ علیہ کے احاطہ مزار میں شاہ جہانی مسجد کے زیر سایہ فضل و کمال کا یہ خزانہ زیر خاک کیا گیا، رحمہما اﷲ تعالیٰ، میر احدی اجمیری نے خوب کہا:
ہے سنہ تیرہ سو انسٹھ (۱۳۵۹) عشرہ ماہ محرم ہے
ہمیں اس ابتدائی ماہ میں بے انتہاغم ہے
امام الوقت مولانامعین الدین کی رحلت ہے
بپا اجمیر میں امسال اُف دوہرا محرم ہے۔
(سید سلیمان ندوی، مارچ ۱۹۴۰ء)

 

اجتہاد کی شرعی حیثیت اور عصر حاضر ميں اجتہاد کی عملی صورتیں

Ijtihad is an invaluable secondary source of the Muslim jurisprudence. In Islamic law, ijtihad refers to the independent interpretation of problems not precisely covered by the sacred scripture of Islam, Qur’an, and Prophetic traditions. The savants who undertake ijtihad must be firmly rooted in knowledge and savvy what the demands of the contemporary era are. Since new challenges call for innovative solutions, the faithful cannot genuinely live by Islam without their jurists deriving the laws of sharia from its sources.

A Co-Relation Study of Telomere Length and Genetic Predisposition to Acute Lymphoblastic Leukemia Among Pakistani Population

Acute lymphoblastic leukemia (ALL) is a hematological malignancy common in children and adult males. ALL is considered to be on the rise in Pakistan. External, physiological and genetic factors have been found to play a fundamental role in causing the cancer. In the present study, we investigated the external factors like exposure to radiations, chemicals, sunlight, smoking, electronic devices and dietary habits as potential risk factors in relation to ALL. None of these factors were found to be associated with ALL risk in Pakistani population. However, among physiological factors we found significant correlation between psychological stress and ALL incidence. Overrepresentation of B+ve blood group was noted among ALL patients. Replicative potential, telomere modulation, migration / metastasis, unlimited proliferation and metabolic reprogramming are important for tumor development. Genes including GMFG, EpCAM, PCSK9, CTC1 and OBFC1 were studied at transcriptional level to elucidate their role in ALL related to motility, proliferation, lipid metabolism and telomere modulation, respectively. The role of these genes in relation to ALL was not studied before. To study telomere modulation important for leukemia cell survival, telomere length measurement was performed. No significant changes in telomere length were observed. However, at transcriptional level, induced expression of telomere modulating genes (CTC1, OBFC1, hTERT) in ALL patients was observed which could be correlated with telomere length maintenance in leukemia cells. The induced GMFG expression, which is important for cell migration, in leukemia patients indicated that it has potential to be used as a leukemia diagnostic marker. EpCAM related to cell proliferation was not well established in ALL. Its mRNA expression was significantly upregulated in ALL patients. Similarly, PCSK9 which regulates cholesterol metabolism was also induced in ALL. mRNA expression of ALL specific genes like TAL1, BLNK and BLACE were also investigated and found to be upregulated in ALL Pakistani population. They, therefore, could potentially be used as ALL gene markers for early detection and diagnosis of leukemia. xii Next, in in vitro studies, naturally occurring biomolecules like costunolide and eugenol were used for identification of new therapeutic approaches with better treatment outcome. Costunolide, a potent telomerase inhibitor reduced EpCAM and its downstream target gene c-Myc and probably also contributed in inhibiting hTERT expression. Similarly, PCSK9 and LOX1 were significantly down-regulated by antioxidant eugenol. Results from this study suggested that costunolide and eugenol could plausibly be used as therapeutic biomolecules for reducing cancer cell proliferation and growth by limiting the metabolic supply.