Sezal1*, Vaibhav Walia2
1Department of Pharmaceutical Sciences MDU Rohtak, Haryana
2Division Pharmacology, G.V.M. College of Pharmacy, Sonepat, Haryana

Depression is a complicated psychiatric disorder characterized by depressed mood, anhedonia, loss of energy and submissive self esteem. Nitric oxide (NO) is the smallest biologically valid molecules which plays an important role in the intracellular signaling. NO negatively controls the levels of 5-HT. Inhibition of NO synthases (NOS) which are responsible for the production of NO; may put in action antidepressants like action. Thus, NO is involved in the pathogenesis of dint and the agents which suppress the NO product exerts antidepressants like effect. Tinospora cordifolia commonly named at the same time that “Guduchi” belonging to family Menispermaceae; has been reported of its persuasive free radical scavenging properties against superoxide anion (O2-), hydroxyl radicals (OH), NO, and peroxynitrite anion (ONOO-). Thus the attempt of the present manuscript is to prove the role of NO in lowness of spirits and how Tinospora cordifolia exerts beneficial personal estate in the patients of depression.


Depression is a intricate psychiatric disorder characterized by depressed vein, anhedonia, loss of energy and cheaply self esteem. Dysregulation of monoaminergic neurotransmitters lay the ~ation of to be involved in the etiology of concavity.[1] The clinical characteristics of indentation include mood changes, hopelessness, depressive episode, psychomotor retardation etc.[2] Stress, is one important risk factor for depression and the pungent stressful life events have been mould to be responsible for the first brunt of depression.[3] Serotonin (5-HT) and norepinephrine are in the first place involved in regulation of mood and emotions and the alteration in the levels and transmission of these neurotransmitters is liable for depression. Thus the lower levels of the 5-HT levels is linked with depression or may increase the vulnerability to depression.[4] Therefore the drugs which correct the alterations in the 5-HT signaling self-reliance be useful in the treatment of stagnation. SSRIs have been used in the manipulation of the depression from the surpassingly long time, these drugs offers unlike each other advantages over the various other categories of the drugs used against the treatment of depression. But the management with the SSRIs increases the venture of suicides in the patients suffering from depression. Therefore there is a unbroken need of newer and safer antidepressants that are free from these life denunciation adverse effects.

Nitric oxide (NO) is the smallest biologically quick molecules which plays an important role in the intracellular signaling. NO serves being of the cl~s who an unconventional messenger molecule in the forcible systems implicated in various cellular processes.[5] NO is synthesized from L-arginine through nitric oxide synthases (NOS). NO is produced ~ dint of. three cell-specific NOS isoforms that are classified according to the chain or cell type in which they were leading found: neuronal nitric oxide synthase (nNOS, NOS-I or Type I), expressed in greatest part brain regions by small populations of neurons, typically GABAergic and besides in skeletal, cardiac and smooth muscles; inducible nitric oxide synthase (iNOS, NOS-II or Type II), initially identified in macrophages and glia; and endothelial nitric oxide synthase (eNOS, NOS-III, NOS-3 or Type III), entirely described in endothelial cells.[6]

Plasma nitrate concentrations were significantly higher in depressed patients, suggesting that the endogenous NO is involved in the pathogenesis of hollow. NO activates soluble guanylyl cyclase, resulting in augment in cGMP levels. [7]cGMP would afterwards activate cGMP-dependent kinase which more distant phosphorylates the 5-HT transporters and enhances the alertness of 5-HT transporter. Thus cGMP mediated enhancement of the etc. of 5-HT transporter results in the contraction in the extracellular level of 5-HT. NO furthermore modulates the release of 5-HT. NO negatively controls the extracellular levels of 5-HT in the hippocampus and the increased combination of NO result in suppression of 5-HT inundate. Inhibition of NO synthase enhances the exercise of antidepressants that work via a serotonergic machinery.[8] Thus the increase in NO fruit following stressful situations can impair serotonergic transmittal in the brain. NO also interact through selective 5-HT re-uptake inhibitors used in the manipulation of depression.[9] NO also modulates 5-HT1A and or 5-HT1B postsynaptic receptor province. Thus NO is involved in the pathogenesis of pit and the agents which suppress the NO produce exerts antidepressants like effect.

Tinospora cordifolia:
Tinospora cordifolia commonly named while “Guduchi” in Sanskrit belonging to family Menispermaceae is a genetically diverse, bulky, deciduous climbing shrub with greenish yellow typical flowers, found at higher altitude. In racemes or racemose panicles, the male animal flowers are clustered and female are isolated. The flowering season expands over summers and winters.[10] Guduchi is furthermore known as Giloe, Giloy, Gurcha (Hindi) and Amrta (Sanskrit). It is institute almost everywhere in India and in Himalayas, smooth up to 1000 feet height. Its area of distribution ranges across a wide region in India spreading from Kumaon Mountains to Kanyakumari. It is furthermore found in China, Myanmar, Sri Lanka, Thailand, Philippines, Indonesia, Malaysia, Borneo, Vietnam, Bangladesh, North Africa, West Africa and South Africa.[11]  A species of active components derived from the put in seed like alkaloids, steroids, diterpenoid lactones, aliphatics, and glycosides obtain been isolated from the different quarters of the plant body, including etymon, stem, and whole plant. Tinospora cordifolia contains alkaloids, glycosides, flavonoids, steroids and terpenoids in the empyrean part of the plant.[11] A kind of constituents used for drug plan have been isolated from the furnish with ~s. They belong to different classes like as alkaloids, diterpenoids lactones, glycosides, steroids, sesquiterpenoides, phenolics, aliphatic compounds, and polysaccharides. The alkaloids tinosporin, tinosporic acid, and tinosporol rich in protein, calcium, and phosphor have been identified in leaves. [12] A copious number of chemicals have been solitary from Tinospora cordifolia, belonging to contrary classes such as alkaloids, diterpenoid lactones, glycosides, steroids, sesquiterpenoid, phenolics, aliphatic compounds and polysaccharides. Leaves of this breed are rich in protein (11.2%), calcium and the morning star.[13] Four new clerodane furano diterpene glucosides (amritosides A, B, C and D) own been isolated as their acetates from stems. The structures of these compounds were established in c~tinuance the basis of spectroscopic studies.[14]

Tinospora cordifolia and Depression:
Tinospora cordifolia extracts reduced the cytokine fruit, mitogenicity, stimulation and activation of immune effector cells.[10]Tinospora cordifolia pull out exerts strong free radical scavenging properties in provision for superoxide anion (O2-), hydroxyl radicals (OH), NO ingrained, and peroxynitrite anion (ONOO-).[10] Petroleum ether determine of Tinospora cordifolia produce antidepressant-like reality by interaction with α1-adrenoceptors, dopamine D2-receptors, serotonergic and GABAB receptors, from this time increasing the levels of norepinephrine, dopamine and serotonin; and decreasing the levels of GABA in understanding of mice.[15]Tinospora cordifolia pull out also reduced the mouse whole brain MAO-A and MAO-B activities taken in the character of compared to control.[15]Tinospora cordifolia select provides protection against oxidative stress, pro-seditious mediator release and redox signaling.  

NO is involved in the pathogenesis of dint and the agents which suppress the NO extension exerts antidepressants like effect. Tinospora cordifolia commonly named of the same kind with Guduchi showed its strong free primitive word scavenging properties against superoxide anion (O2-), hydroxyl radicals (OH), NO, and peroxynitrite anion (ONOO-). Tinospora cordifolia cite provides protection against oxidative stress, pro-incendiary mediator release and redox signaling.  Thus it has been concluded that the Tinospora cordifolia exerts beneficial import in the depression through its NO scavenging exercise.

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12. Antonisamy P, Dhanasekaran M, Ignacimuthu S, Duraipandiyan V, Balthazar JD, Agastian P, Kim JH. Gastroprotective reality of epoxy clerodane diterpene isolated from Tinospora cordifolia Miers (Guduchi) without ceasing indomethacin-induced gastric ulcer in rats. Phytomedicine. 2014 Jun 15;21(7):966-9.
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