Presentation On Preclinical Evaluation of Tinospora cordifolia L.

Bark Extract as Neuroprotective Agent for its application in CNS Cognition Studies

For the degree Master in pharmacy in Pharmacology

PRESENTED BY

Abhishek Joshi

SUPERVISOR CO-SUPERVISOR

DR.Mahendra Rana DR. A.K. Mishra

(Assistant Professor) (HOD & Jt.Director)

Department of Pharmaceutical sciences INMAS(DRDO)

Bhimtal Campus, Kumaun University DELHI

INTRODUCTION

Memory function is vulnerable to a variety of pathologic processes including neuro- degenerative diseases, hypoxia, attention-deficit disorder, depression, anxiety .

Learning and memory are generated by an experience dependent

and long-lasting modification of the central nervous system.

They involve activation by neurotransmitters, such as, acetylcholine, dopamine, and serotonin, of the receptor-linked enzymes

A large number of studies shows that the cholinergic system plays an important role in learning and memory loss of cholinergic neurons

Reduced choline- acetyltransferase activity in the cerebral cortex and hippocampus are consistent with findings in Neurodegenerative disorder(ND) .

Reduced cholinergic activity in the brains of individuals with ND provides the rationale for the development of acetyl cholinesterase (AChE) inhibitors to treat ND.

NEUROTRANSMITTERS

Neurotransmitters are chemicals that transmit information from one nerve cell (neuron) to another. “They are defined as chemical transducers which are released by electrical impulse into the synaptic cleft from presynaptic membrane from synaptic vesicles. It then diffuses to the postsynaptic membrane and reacts and activates the receptors present leading to initiation of new electrical signals.”

Neurotransmitter Function: Enzymes involved in synthesis

Acetylcholine mostly excitatory Choline acetyltransferase

Bioactive amines

Dopamine excitatory and inhibitory Tyrosine hydroxylase

Epinephrine excitatory Tyrosine hydroxylase and dopamine-

b-hydroxylase

Nor -epinephrine excitatory Tyrosine hydroxylase and dopamine-

b-hydroxylase

Serotonin excitatory Tryptophan hydroxylase

Amino acids

Glutamate excitatory Metabolic amino acid

Glycine mostly inhibitory Metabolic amino acid

ý-Aminobutyric

acid (GABA) inhibitory Glutamate decarboxylase

PLANT UNDER STUDY

PLANT PROFILE• Tinospora cordifolia, which is known by the common name Guduchi, is a

herbaceous wine of the family Menispermaceae indigenous to the tropical areas of India, Myanmar and Sri lanka. The plant is a glabrous climbing shrub found throughout India, typically growing in deciduous and dry forests.

• Tinospora cordifolia has greenish flowers, fruits are shiny fleshy, pea shaped, which occurs in winters and the entire plant is used medicinally.

Taxonomical classification• Kingdom: Plantae• Division: Magnoliophyta• Class: Magnoliopsida • Order: Ranunculales• Family: Menispermaceae• Genus: Tinospora• Species: cordifolia • Synonym: Hindi: giloe, Sanskrit: Amritavalli, Marathi: Guduchi , • Binomial name : - Tinospora cordifolia

Ethno-Pharmacological uses/actions:

Anti-diabetic Anti-inflammatory Anti-arthriticAnti-oxidant Anti-allergic Anti-stress Anti-malarialHepatoprotective Anti-neoplastic activities

 

AIM AND OBJECTIVE Aim:

The aim of the investigation is radiolabelling of Tinospora cordifolia bark extract and evaluating its neuroprotective agent for application in CNS cognition studies.

1. Preliminary investigation carried out determining the ability of selected doses of a plant bark extract.

2. The test material subjected to various parameters like optimization of labeling conditions, quality control, PH Study parameter, drug- stability, blood-kinetics and bio-distribution studies.

Objectives:

The principle objective of study:- o Alteration in neurotransmitters level in pre-treated (Irradiation treated)

mice. o Alteration in neurotransmitters level in post-treated(Irradiation+ Extract

treated) mice.

S.No Authors Year Contributions

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

Mathew S. et al

Jain Giri. et al

Singla A. et al

Sarma DNK. et al

Goel HC. et al

Singh SS. et al

Pahadiya S. et al

Prince PSM. et al

Agarwal. et al

Bishayi B. et al

2011

2010

2010

2005

2004

2003

2003

2003

2002

2002

Reported Antioxidant activity of Tinospora cordifolia and its usefulness in the cyclophosphamide induced toxicity. Reviewed the antipsychotic activity of aqueous ethanolic extract of Tinospora cordifolia in amphetamine challenged mice model.Reported the biological activities of T. cordifolia extract(s) on different animal models as well as on human beings.Studied the effect of T. cordifolia on brain neurotransmitters in stressed rats. Reported radioprotective potential of an herbal extract of T. cordifolia and evaluated its radioprotective efficacy.

Reported the anti-stress and tonic property of plant.

Reported the alteration of lethal effects of gamma rays in swiss albino mice by Tinospora cordifolia. Reported the hypogycaemic and hypolipidaemic action of alcohol extract of T. cordifolia roots .Reported the effect of T. cordifolia on learning and memory Deficit rats .Reported the hepatoprotective and immunomodulatory properties of T. cordifolia in CCL4 intoxicated mature albino rats.

LITERATURE REVIEW

WORK DONE

1.Tinospora cordifolia barks were collected from the hilly region of Uttarakhand.

2. The extraction of the bark sample was done under the guidance and supervision of Dr. Hemant Kumar

Pande(DIBER,Pithoragarh).

3. The extract obtained was then evaluated for the presence of active constituents present in it.

4. The extract was radiolabelled with technetium-99m.

5. The radiolabelling efficiency of the extract was evaluated.

6.The radiolabelled herbal extract was injected to female mice and radiolabelling Studies were performed.

7.Pharmacokinetics Study of herbal extract was performed and drug clearance rate was identified.

PROPOSED PLANS PROPOSED PLANS

In Vitro Animal Studies

Comparative Study Of Radiolabelled Herbal Extract With Standard Drug(Piracetam)

Brain Uptake Studies

Bio Distribution(Organ) Studies.

In Vitro Animal Studies

Comparative Study Of Radiolabelled Herbal Extract With Standard Drug(Piracetam)

Brain Uptake Studies

Bio Distribution(Organ) Studies.

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