Gireesh Kumar Singh

Antidepressant activity of Asparagus racemosus in rodent models

Asparagus racemosus Linn. (AR) is an Ayurvedic rasayana used as an adaptogen. Adaptogenic drugs are those which are useful as anti-stress agents by promoting non-specific resistance of the body. Although, the adaptogenic effect of AR is well documented, its use in psychological disorders like depression is not scientifically evaluated. Hence, the present investigation evaluates the antidepressant effect of methanolic extract of roots of AR (MAR) standardized to saponins (62.2% w/w). Rats were given MAR in the doses of 100, 200 and 400 mg/kg daily for 7 days and then subjected to forced swim test (FST) and learned helplessness test (LH). The results show that MAR decreases immobility in FST and increases avoidance response in LH indicating antidepressant activity. In behavioral experiments, MAR increased the number of head twitches produced by 5-HTP and increased clonidine-induced aggressive behavior indicating facilitatory effect on both serotonergic and adrenergic systems respectively. However, MAR had insignificant effect on l-DOPA-induced aggressive behavior indicating absence of activity on dopaminergic system. MAR also reversed changes to the endogenous antioxidant system induced by FST. Thus, MAR has significant antidepressant activity and this effect is probably mediated through the serotonergic and the noradrenergic systems and augmentation of antioxidant defenses.

Asparagus recemosus enhances memory and protects against amnesia in rodent models

Asparagus Racemosus (AR) is an Ayurvedic rasayana possessing multiple neuropharmacological activities. The adpatogenic and antidepressant activity of AR is well documented. The present study was undertaken to assess nootropic and anti-amnesic activities of MAR in rats. The Morris water maze (MWM) and elevated plus maze (EPM) models were employed to evaluate learning and memory activity. Subsequently, the anti-amnestic activity was evaluated in scopolamine and sodium nitrite (NaNO(2))-induced amnestic models in rats. Rats pre-treated with MAR (50, 100 and 200mg/kg, p.o) for 7 days showed significant decrease in escape latency in the MWM test indicating nootropic activity. MAR also significantly reversed scopolamine and sodium nitrite-induced increase in transfer latency on EPM indicating anti-amnesic activity. Further, MAR dose-dependently inhibited acetylcholinesterase enzyme in specific brain regions (prefrontal cortex, hippocampus and hypothalamus). Thus, MAR showed nootropic and anti-amnesic activities in the models tested and these effects may probably be mediated through augmentation of cholinergic system due to its anti-cholinesterase activity.

Acute and sub-chronic toxicity study of standardized extract of Fumaria indica in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE Despite Fumaria indica (FI) widespread medicinal uses in the Indian traditional medicine, no systematic study of the potential toxicity of the plant has been described. AIM OF THE STUDY To assess acute and sub-chronic toxicity of a 50% ethanolic extract of FI in mice and rats respectively. MATERIALS AND METHODS In acute toxicity study, Swiss strain albino mice of either sex were administered orally FI doses of 1, 2.5 and 5 g/kg and observed for behavioural changes and mortality, if any. In sub-chronic toxicity study, Charles Foster albino rats of either sex were administered two doses of FI i.e., 100 and 400mg/kg, p.o. for 30 consecutive days. During 30 days of treatment, rats were observed for any change in body weight and daily food and water intake. After 30 days, rats were sacrificed for haematological, biochemical and histopathology study. Control animals were administered 0.3% carboxymethyl cellulose (CMC) suspension by oral route. RESULTS There was no mortality or abnormal behaviour, observed in acute toxicity study in mice at all the three dose levels. In sub-chronic toxicity study, FI did not produce any significant change in body weight and daily food and water intake of rats when compared to vehicle treated rats. Further, haematological and biochemical parameters were also found normal. Histopathological study revealed normal architecture of kidney and liver of FI treated rats. CONCLUSIONS FI extract, provisionally standardized on its fumarate contents, seems to fulfill a preclinical criterion necessary for its further development as a clinically useful adaptogen.

A review on pharmacological and analytical aspects of naringenin

Flavonoids are a widely distributed group of phytochemicals having benzo-pyrone nucleus, and more than 4,000 different flavonoids have been described and categorized into flavonols, flavones, flavanones, isoflavones, catechins and anthocyanidins. Flavonoids occurs naturally in fruits, vegetables, nuts, and beverages such as coffee, tea, and red wine, as well as in medical herbs. Flavonoids are responsible for the different colors of plant parts and are important constituents of the human diet. Flavanoids have different pharmacological activities, such as antioxidant, anti-allergic, antibacterial, anti-inflammatory, antimutagenic and anticancer activity. Naringenin belongs to the flavanones and is mainly found in fruits (grapefruit and oranges) and vegetables. Pharmacologically, it has anticancer, antimutagenic, anti-inflammatory, antioxidant, antiproliferative and antiatherogenic activities. Naringenin is used for the treatments of osteoporosis, cancer and cardiovascular diseases, and showed lipid-lowering and insulin-like properties. In the present review, detailed pharmacological and analytical aspects of naringenin have been presented, which revealed the impressive pharmacological profile and the possible usefulness in the treatment of different types of diseases in the future. The information provided in this communication will act as an important source for development of effective medicines for the treatment of various disorders.

Role of fumaric acid in anti-inflammatory and analgesic activities of a Fumaria indica extracts.

Aim: The aim was to test whether the ethanolic extract of Fumaria indica (FI) possesses anti-inflammatory and analgesic activities, and fumaric acid (FA) could be one of its bioactive constituent involved in such activities of the extract. Materials and Methods: For anti-inflammatory activity, carrageenan-induced edema and cotton pellet induced granuloma tests in rats and for analgesic activity rat tail flick test and hot plate and acetic acid writhing tests in mice were used. All tests were performed after seven daily oral doses of the FI extract (100, 200, and 400 mg/kg/day) and pure FA (1.25, 2.50, and 5.00 mg/kg/day). Results: Anti-inflammatory activities of FI and FA were observed in carrageenan-induced edema and cotton pallet granuloma even after their lowest tested doses. No analgesic activity of lowest tested dose of FA was observed in the acetic acid writhing test, but likewise, all tested dose levels of FI, higher tested dose levels of FA were also possess significant analgesic activity in this test. Further, significant analgesic activities of both FI and FA in hot plate and tale flick tests were observed after all their tested doses. Conclusions: These observations are in agreement with our working hypothesis on the connection of FA in mode(s) of action(s) of FI, and reaffirm the conviction that FI could be an herbal alternative against fibromyalgia and other pathologies often associate with, or caused by, inflammatory processes.

Design, synthesis, characterization, and molecular modeling studies of novel oxadiazole derivatives of nipecotic acid as potential anticonvulsant and antidepressant agents

A series of fifteen novel nipecotic acid 1,3,4-oxadiazole hybrids were synthesized with the intent to improve the lipophilicity of nipecotic acid and its penetration through the blood—brain barrier (BBB). The structures of the compounds were established by FT-IR, 1H-NMR, 13C-NMR, and elemental analysis. The effect of the synthesized compounds was assessed on motor coordination using the rotarod test in mice. Anticonvulsant activity was evaluated using the subcutaneous pentylenetetrazol (scPTZ) test in mice. Five compounds (5d, 5e, 5g, 5m, and 5o) exhibited significant protection against scPTZ-induced seizures. None of the compounds produced any disruption in motor coordination as observed in the rota-rod test, nor did they elevate the serum levels of biochemical markers related to hepatic and renal toxicity, affirming their relative safety. The derivatives also exhibited significant antidepressant activity, devoid of serotonergic augmentation as assessed using the despair swim test, 5-hydroxytryptophan (5-HTP)-induced head twitch test and learned helplessness test. In in silico docking studies on a homology model on target GABA transporter 1 (GAT1) protein and the most active compound 5e helped to identify critical enzyme-ligand interactions leading to the inhibition of the GAT1 transporter.

Wound healing activity of the ethanol root extract and polyphenolic rich fraction from Potentilla fulgens

Abstract Context: Potentilla fulgens Wall. ex Hook (Rosaceae) is a potent medicinal plant of the Western Himalayas, where its roots are traditionally used by the local people of Uttaranchal (India) to treat wounds and tiger bites. Objective: The present study scientifically evaluates the wound healing activity of P. fulgens ethanol root extract (EPF) and its ethyl acetate fraction (PFEA) on experimental rats. Materials and methods: Wounds were inflicted on animals by using both excision and incision models. The wounded animals were treated for 16 days with EPF (oral: 200–400 mg/kg and topical: 5–10% w/w) and PFEA (oral: 75 mg/kg; topical: 1.75% w/w). Various physical (wound contraction, epithelialization rate, tensile strength) and biochemical parameters (hydroxyproline, hexosamine, proteins, DNA) were examined during the study. Oxidant product (lipidperoxidase), antioxidant enzymes (catalase, superoxide-dismutase) and reduced glutathione were determined. Morphological and histopathological studies of the skin tissues were monitored. Results: A significant (p < 0.05) wound healing property was observed when the animals were treated topically with EPF (10% w/w) and PFEA (1.75% w/w). A significantly (p < 0.05) increased in the levels of hydroxyproline, hexosamine, protein and DNA up to 59.22, 70.42, 61.01 and 60.00% was observed, respectively. This effect was further demonstrated by the morphological and histopathological representation, thus showing significant (p < 0.05) re-epethelialization on the healing area. EPF and PFEA also showed significant (p < 0.05) antioxidant activity. Conclusions: The present study provided the scientific evidence, where P. fulgens rich in polyphenolic components possess remarkable wound healing activities, thereby supporting the traditional claims.

A review on medicinal uses, analytical techniques and pharmacological activities of Strychnos nux-vomica Linn.: A concise report

The purpose of this review is to provide comprehensive and relevant information on the utilization and pharmacological activities of Strychnos nux-vomica Linn. (Loganiaceae), used for the treatment of various diseases. Strychnos nux-vomica is an evergreen tree native to Southeast Asia and its dried seeds are used for the treatment of neurodisorders, arthritis and vomiting. The different use of this plant as herbal remedy in Chinese medicine is also reported in the literature. Strychnine and brucine are major pharmacologically active phytoconstituents of Strychnos nux-vomica, which are central nervous stimulant, but also found to be poisonous at high dosage. Owing to its diversity of phytoconstituents, it is used for treatment of various disorders. Pharmacologically it has been validated for its effect on inflammation, microbial infections, gastrointestinal problem, nervous system, bones cells, cardiovascular systems, cancer and blood glucose level. It also has antioxidant activity and antifeedant activity. Informations about Strychnos nux-vomica, compiled in the present review article could be useful to the researchers for the scientific validation of its traditional claim in the future.

Preliminary Screening of a Classical Ayurvedic Formulation for Anticonvulsant Activity

Background: Epilepsy is a serious and complex central nervous system disorder associated with recurrent episodes of convulsive seizures due to the imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) neurotransmitters level in the brain. The available treatments are neither competent to control the seizures nor prevent progress of disease. Since ages, Herbal medicines have remained important sources of medicines in many parts of world which is evidenced through their uses in traditional systems of medicine i.e. Ayurveda, Siddha, Unani, Homeopathy and Chinese etc. Aim: A polyherbal formulation (containing Terminalia chebula Retz., Asparagus racemosus Willd., Embelia ribes Burm. F, Acorus calamus L., Tinospora cordifolia (Willd.) Miers, Convolvulus pluricaulis Choisy, Saussurea lappa C.B.Clarke, Achyranthes aspera L.) is mentioned in Ayurvedic classics Bhaiṣajya Ratnāvali. The aim of the study was to evaluate the anticonvulsant activity of the formulation in Maximum electroshock and Pentylenetetrazole induced convulsions in rats. Materials and Methods: In the present study, a polyherbal formulation was developed as directed by classical text and evaluated for the anticonvulsant activity using Maximal Electroshock Shock (MES) and Pentylenetetrazole (PTZ) induced convulsions in rats. Statistical comparison was done by one way ANOVA followed by the Tukeys multiple comparison test. Results: The obtained results showed that the PHF had a protective role on epilepsy. Treatment with PHF significantly improves antioxidant enzymes activities of superoxide dismutase (SOD) and glutathione (GSH) levels significantly as compared to controls. PHF also significantly decreased malonaldialdehyde (MDA) levels in the brain. Moreover, it also attenuated the PTZ-induced increase in the activity of GABA-T in the rat brain. Conclusion: These findings suggest that PHF might have possible efficacy in the treatment of epilepsy.