Shakti Deep Pachauri
Central Drug Research Institute
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Featured researches published by Shakti Deep Pachauri.
Journal of Ethnopharmacology | 2012
Shakti Deep Pachauri; Santoshkumar Tota; Kiran Khandelwal; Priya Ranjan Prasad Verma; Chandishwar Nath; Kashif Hanif; Rakesh Shukla; J.K. Saxena; Anil Kumar Dwivedi
ETHNOPHARMACOLOGICAL RELEVANCE Noni (Morinda citrifolia L.) is widely used for different illnesses including CNS disorders. Recently Noni has been reported to prevent amyloid beta induced memory impairment in mice. However, the influence of Noni on cholinergic system has not been explored so far. Therefore, present study was designed to investigate effect of Noni fruit on memory, cerebral blood flow (CBF), oxidative stress and acetylcholinesterase (AChE) activity in scopolamine induced amnesia model. MATERIALS AND METHODS Mice were orally treated with ethanolic extract of Noni fruit and chloroform, ethyl acetate and butanol fractions of ethanolic extract for three days. Scopolamine was administered 5 min prior to acquisition trial and memory function was evaluated by passive avoidance test. CBF was measured by laser doppler flowmetry. AChE activity and oxidative stress parameters were estimated in mice brain at the end of behavioral studies. Further, effect of ethanolic extract and its fractions (5-400 μg/ml) on AChE activity was measured in vitro. RESULTS Scopolamine caused memory impairment along with reduced CBF, increased AChE activity and oxidative stress in mice brain. Ethanolic extract of Noni fruits and its chloroform and ethyl acetate fractions significantly improved memory and CBF. However, butanol fraction had no effect. Further, increased oxidative stress and AChE activity following scopolamine was significantly attenuated by ethanolic extract of Noni and its fractions. Moreover ethanolic extract and its fractions showed dose dependent inhibition of AChE activity in vitro. CONCLUSION These observations suggest that Noni may be useful in memory impairment due to its effect on CBF, AChE and oxidative stress.
Behavioural Pharmacology | 2013
Shakti Deep Pachauri; Priya Ranjan Prasad Verma; Anil Kumar Dwivedi; Santoshkumar Tota; Kiran Khandelwal; Jitendra K. Saxena; Chandishwar Nath
This study evaluated the effects of a standardized ethyl acetate extract of Morinda citrifolia L. (Noni) fruit on impairment of memory, brain energy metabolism, and cholinergic function in intracerebral streptozotocin (STZ)-treated mice. STZ (0.5 mg/kg) was administered twice at an interval of 48 h. Noni (50 and 100 mg/kg, postoperatively) was administered for 21 days following STZ administration. Memory function was evaluated using Morris Water Maze and passive avoidance tests, and brain levels of cholinergic function, oxidative stress, energy metabolism, and brain-derived neurotrophic factor (BDNF) were estimated. STZ caused memory impairment in Morris Water Maze and passive avoidance tests along with reduced brain levels of ATP, BDNF, and acetylcholine and increased acetylcholinesterase activity and oxidative stress. Treatment with Noni extract (100 mg/kg) prevented the STZ-induced memory impairment in both behavioral tests along with reduced oxidative stress and acetylcholinesterase activity, and increased brain levels of BDNF, acetylcholine, and ATP level. The study shows the beneficial effects of Noni fruit against STZ-induced memory impairment, which may be attributed to improved brain energy metabolism, cholinergic neurotransmission, BDNF, and antioxidative action.
Pharmaceutical Biology | 2015
Gurpreet Kaur; Neetu Singh; Sheeba Saji Samuel; Himangshu K. Bora; Sharad Sharma; Shakti Deep Pachauri; Anil Kumar Dwivedi; Hefazat Hussain Siddiqui; Kashif Hanif
Abstract Context: Withania somnifera (Linn.) Dunal (Solanaceae), a clinically used herbal drug in Ayurveda, shows potent antioxidant, anti-inflammatory, pro-apoptotic, and cardioprotective effects. However, the efficacy of W. somnifera in pulmonary hypertension (PH), a cardiopulmonary disorder, remains unexplored. Objective: The present study investigates the effect of W. somnifera root powder on monocrotaline (MCT)-induced PH in rats. Materials and methods: In preventive studies, W. somnifera root powder (50 and 100 mg/kg/d, p.o.) was administered from day 1 following single administration of MCT (60 mg/kg, s.c.) in Sprague–Dawley (SD) rats. After 35 d, right ventricular pressure (RVP) was measured in anesthetized rats. Various physical markers of right ventricular hypertrophy (RVH) were measured in isolated hearts. Markers of endothelial function, inflammation, and oxidative stress were estimated in lung homogenate. Vasoreactivity of pulmonary arteries was also studied. In therapeutic treatment, W. somnifera (50 and 100 mg/kg/d, p.o.) was administered from day 21 to 35 post-MCT administration. Results: Preventive treatment with 50 and 100 mg/kg W. somnifera significantly reduced the RVP (32.18 ± 1.273 mm Hg and 29.98 ± 1.119 mm Hg, respectively, versus 42.96 ± 1.789 mm Hg of MCT) and all markers of RVH in MCT-challenged rats. There was an improvement in inflammation, oxidative stress and endothelial dysfunction, and attenuation of proliferative marker and apoptotic resistance in lungs. Therapeutic treatment with W. somnifera (100 mg/kg) also reduced RVP and RVH. Discussion: This study demonstrated that W. somnifera significantly protected against MCT-induced PH due to its antioxidant, anti-inflammatory, pro-apoptotic, and cardioprotective properties.
Drug Research | 2015
Komal Sharma; Shakti Deep Pachauri; Kiran Khandelwal; Hafsa Ahmad; Abhishek Arya; P. Biala; S. Agrawal; R. R. Pandey; A. Srivastava; A. Srivastav; Jitendra Kumar Saxena; Anil Kumar Dwivedi
Morinda citrifolia L. (NONI) fruits have been used for thousands of years for the treatment of many health problems including cancer, cold, diabetes, flu, hypertension, and pain. Plant extracts have reported several therapeutic benefits, but extraction of individual compound from the extract often exhibits limited clinical utility as the synergistic effect of various natural ingredients gets lost. They generally constitute polyphenols and flavonoids. Studies have suggested that these phytochemicals, especially polyphenols, display high antioxidant properties, which help to reduce the risk of degenerative diseases, such as cancer and cardiovascular diseases. Several in-vitro and in-vivo studies have shown that Noni fruits have antioxidant, anti-inflammatory, anti-dementia, liver-protective, anticancer, analgesic, and immunomodulatory effects. Till date about 7 in vitro cancer studies have been done, but a detailed in vitro study including cell cycle and caspase activation assay on breast cancer cell line has not been done. In the present study different Noni fruit fractions have tested on cancer cell lines MCF-7, MDA-MB-231 (breast adenocarcinoma) and one non-cancer cell line HEK-293 (Human embryonic kidney). Out of which ethylacetate extract showed a higher order of in vitro anticancer activity profile. The ethylacetate extract strongly inhibited the proliferation of MCF-7, MDA-MB-231 and HEK-293 cell lines with IC50 values of 25, 35, 60 µg/ml respectively. The extract showed increase in apoptotic cells in MCF-7 and MDA-MB-231 cells and arrested the cell cycle in the G1/S phase in MCF-7 and G0/G1 phase in MDA-MB-231 cells. Noni extract also decreases the intracellular ROS generation and mitochondrial membrane potential.
Pharmacognosy Magazine | 2014
Hafsa Ahmad; Kiran Khandelwal; Shakti Deep Pachauri; Rajender Singh Sanghwan; Anil Kumar Dwivedi
Background: Withania somnifera Dunal (Ashwagandha) is an Indian medicinal plant of great medicinal value; used in many clinically proven conditions. NMITLI-118RT+ is a candidate drug under a Council of Scientific and Industrial Research (CSIR) networking project. It is a chemotype of W. somniferas root extract, which has been used for the present study. Objectives: The present investigation aims to develop and validate a simple isocratic reverse phase-high performance liquid chromatography (RP-HPLC) system for the detection and estimation of Withanolide A (marker compound) and its analytical application for stability indicating studies on NMITLI-118RT+. Material and Methods: A validated RP-HPLC method for Withanolide A was established on a Waters HPLC system and the same was used on NMITLI-118RT+ for quantification and fingerprinting purposes, and for establishing forced degradation, isothermal stress tests, and drug-excipient testing protocols as per International Conference on Harmonization (ICH) guidelines. Results: A validated method was established, which could detect the marker at a retention time of around 6.3 minutes, with a linearity range of 2-100 μg/mL, by varying the amounts of the said marker, which were estimated in four different batches of NMITLI-118RT+. Photostability as per ICH guidelines suggested a slight loss of the active constituent and maximum degradation was afforded with alkali followed by acid, and then peroxide, in the forced degradation studies. In the drug-excipient studies, the maximum amount of active constituent could be detected in the samples with ethyl cellulose and the least with hydroxy propyl cellulose. Conclusion: The method developed here was simple and rapid. The various stability indicating studies carried out in the present investigation would be useful for formulation development and were suggestive of deciding the recommended storage conditions for NMITLI-118RT+.
Drug Delivery | 2016
Varsha Gupta; Swati Singh; Madhumita Srivarstava; Hafsa Ahmad; Shakti Deep Pachauri; Kiran Khandelwal; Pankaj Dwivedi; Anil Kumar Dwivedi
Abstract This research aims at the development of controlled release contraceptive transdermal patches of centchroman using ethylcellulose (EC) as film-forming polymer, polydimethylsiloxane (PDMS) as pressure sensitive adhesive with propylene glycol and Di-n-butyl-phthalate for their penetration enhancer and plasticizing properties, respectively. The physicochemical compatibility of the drug and the polymers was performed by differential scanning calorimetry and Fourier transform infrared (FTIR) spectroscopic technique. Effects of EC and PDMS ratios on moisture uptake, moisture content, tensile strength (TS), Young’s modulus, adhesive strength, water vapor transmission rate (WVTR) and in vitro permeation of centchroman through Sprague–Dawley rats abdominal skin using Franz’s diffusion cell were evaluated. A 32 full factorial design was employed to observe the effect of independent variables; concentration of ethyl cellulose and PDMS on drug permeated after 32 h, which was selected as dependent variable. Compatibility studies suggested that there were no significant interaction between the drug and polymers used. It was found that incorporation of only EC resulted in too hard patches and addition of PDMS produced patches with lower TS, increased percentage elongation, WVTR and Young’s modulus. Statistical analyses suggested that independent variables have a significant effect on the dependent variable. All formulation follows zero-order release kinetics with r2 > 0.990. In conclusion, drug in adhesive transdermal patches can be successfully fabricated for non-steroidal contraceptive centchroman to obtain a zero-order release systems.
Bioorganic & Medicinal Chemistry Letters | 2014
Rishi Ranjan Pandey; Akansha Srivastava; Shakti Deep Pachauri; Kiran Khandelwal; Arshi Naqvi; Richa Malasoni; Bhavana Kushwaha; Lokesh Kumar; Jagdamba P. Maikhuri; Garima Pandey; Sarvesh Paliwal; Gopal Gupta; Anil Kumar Dwivedi
A series of γ-butyrolactone derivatives has been designed and synthesized from commercially available 2-acetyl butyrolactone (3-acetyldihydrofuran-2(3H)-one, 1) by aminoalkylating its active methylene followed by condensation with different aldehydes. Compounds having amino group were further converted to their respective tartrate salts and were evaluated for spermicidal activity against human sperm in vitro. Compounds showing appreciable spermicidal activity at ⩽0.5% [3c, 4d (0.5%); 2c, 3d (0.1%); 2d, 4c (0.05%)] were tested for safety studies against human cervical (HeLa) cell line. These compounds were found safer than, Nonoxynol-9. One of the two most active compounds was also found to be the safest (IC50=961 μg/ml; 4c), while the second compound exhibited lower safety against HeLa (IC50=269 μg/ml; 2d). The compound 4c significantly reduced the number of free thiols on human sperm. All the compounds were inactive against Trichomonas vaginalis.
RSC Advances | 2015
Kiran Khandelwal; Shakti Deep Pachauri; Abhishek Arya; Vivek K. Pawar; Trapti Joshi; Pankaj Dwivedi; Hafsa Ahmad; Bhupendra N. Singh; Komal Sharma; Sanjeev Kanojiya; Manish K. Chourasia; Anil K. Saxena; Anil Kumar Dwivedi
S002-333, a novel anti-thrombotic agent, exhibits excellent platelet mediated antithrombotic action and subsequently has no effect on the coagulation cascade. However, its oral bioavailability is hampered due to inherent low aqueous solubility. In order to circumvent this issue, chitosan coated liposomes were prepared by an ethanol injection method. S002-333 loaded liposomes (CH-LIP-F9) were reproduced with homogeneous particle sizes. The liposomal formulation was characterized with respect to size and surface morphology by transmission electron microscopy (TEM). The optimized formulation exhibited spherical shapes with a nano-metric size (249.64 ± 10.36 nm). The percentage entrapment efficiency (% EE) offered by the various developed formulations was found to be in the range between 72.36 ± 1.76 and 76.87 ± 2.32%. An in vitro release experiment demonstrated prolonged release of S002-333 from the optimized liposomal formulation. A cytotoxicity study represented that both blank liposomes (BLK-LIP) as well as the drug bearing liposomal formulation displayed negligible toxicity towards Caco-2 cells. The results of a pharmacokinetic study indicated that liposomal formulation significantly enhanced oral absorption of S002-333 in rats (AUC0–t; 7016.02 ± 128.96 h ng mL−1) compared to its aqueous suspension (AUC0–t; 2382.02 ± 77.17 h ng mL−1). These results together elicited that the developed liposomal formulation would improve preclinical and clinical application of S002-333.
Journal of Pharmaceutical Analysis | 2013
Kiran Khandelwal; Shakti Deep Pachauri; Sofia Zaidi; Pankaj Dwivedi; Ashok Kumar Sharma; Chandan Singh; Anil Kumar Dwivedi
CDRI compound no. 99/411 is a potent 1,2,4-trioxane antimalarial candidate drug under development at our Institute. An HPLC method for determination of CDRI 99/411 with its starting material and intermediates has been developed and validated for in process quality control and stability studies. The analytical performance parameters such as linearity, precision, accuracy, specificity, limit of detection (LOD) and lower limit of quantification (LLOQ) were determined according to International Conference on Harmonization ICH Q2(R1) guidelines. HPLC separation was achieved on a RP-select B Lichrosphere® column (250 mm×4 mm, 5 μm, Merck) using water containing 0.1% glacial acetic acid and acetonitrile as the mobile phase in a gradient elution. The eluents were monitored by a photo diode array detector at 245 and 275 nm. Based on signal to noise ratio of 3 and 10 the LOD of CDRI 99/411 was 0.55 µg/mL, while the LLOQ was 1.05 µg/mL. The calibration curves were linear in the range of 1.05–68 µg/mL. Precision of the method was determined by inter- and intra-assay variations within the acceptable range.
Psychopharmacology | 2013
Santoshkumar Tota; Ruby Goel; Shakti Deep Pachauri; N. Rajasekar; Abul Kalam Najmi; Kashif Hanif; Chandishwar Nath