Browsing by Author "Rashmi Shukla"

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Acute and sub-acute toxicity study of hydro-alcoholic leaves extract of Reinwardtia indica in rats
(Elsevier Masson SAS, 2019) Prabhat Upadhyay; Rashmi Shukla; Sunil Kumar Mishra
The present study was to assess the toxicity of hydro alcoholic leaves extract of Reinwardtia indica in Charles foster rats through an acute and sub-acute study. In the acute study, rats were treated orally with single dose and for sub-acute study different doses were given orally for 28 consecutive days. At the dose of 2000 mg/kg satellite group was also used for 6 weeks as per OECD guidelines-407. General behavioral parameters were assessed in acute toxicity and found no mortality or exterior signs of toxicity. While in the sub-acute study; biochemical, hematological and histopathology along with the body weight, food, and water consumptions parameters were screened in the animals after 14 & 28 days. The study reveals the insignificant (P < 0.05) change in treated group in comparison to the control. The hydroalcoholic leaves extract of Reinwardtia indica was found non-toxic up to 5000 mg/kg in acute study whereas up to 2000 mg/kg dose level in the sub-acute study. © 2018 Elsevier Masson SAS
An extract of Pueraria tuberosa tubers attenuates diabetic nephropathy by upregulating matrix metalloproteinase-9 expression in the kidney of diabetic rats
(John Wiley and Sons Inc., 2017) Yamini B. Tripathi; Rashmi Shukla; Nidhi Pandey; Vivek Pandey; Mohan Kumar
Background: Currently, no drug is available to directly target the signaling molecules involved in the pathogenesis of diabetic nephropathy (DN); only antihypertensive and antidiabetic drugs are in clinical use. In the present study, the therapeutic effects of a active fraction of tubers from Pueraria tuberosa (hereafter referred to as PTY-2) were investigated in streptozotocin (STZ)-diabetic rats with DN, with particular emphasis on its effects on extracellular matrix (ECM) accumulation and matrix metalloproteinase (Mmp)-9 expression in kidney tissue. Methods: Rats were injected with 55 mg/kg, i.p., STZ. After 40 days, rats were divided into groups as follows (n = 6 per group): Group 1, age-matched rats not injected with STZ (non-diabetic control); Group 2, STZ-diabetic DN rats; and Group 3, PTY-2 (30 mg/100 g, p.o.)-treated DN rats. After 20 days treatment, the effects of PTY-2 on serum urea and creatinine concentrations, urinary levels of glucose, creatinine, protein, and ketone bodies, and urine pH were determined. Kidney tissue was evaluated for Mmp-9 expression and histological changes. Results: Blood glucose, serum urea, creatinine, and urine protein levels were significantly higher, and creatinine clearance was significantly lower, in Group 2 versus Group 1 rats. There was a higher degree of glomerulosclerosis, expansion of the mesangial matrix, and excess ECM deposition and eosinophilic casts in kidneys from Group 2 versus Group 1 rats. Furthermore, Mmp-9 activity and expression were significantly reduced in kidney homogenate of Group 2 versus Group 1 rats. Interestingly, PTY-2 treatment significantly reversed all these changes in DN rats. Conclusion: Treatment of DN rats with PTY-2 significantly attenuated the severity of DN by increasing the expression and activity of Mmp-9, consequently degrading the ECM accumulated in kidney tissue. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd
Antioxidant and Antiapoptotic effect of aqueous extract of Pueraria tuberosa (Roxb. Ex Willd.) DC. On streptozotocin-induced diabetic nephropathy in rats
(BioMed Central Ltd., 2018) Rashmi Shukla; Somanshu Banerjee; Yamini B. Tripathi
Background: Oxidative stress and renal apoptosis play a significant role in the progression of diabetic nephropathy. The tubers of Pueraria tuberosa (Roxb. ex Willd.) DC. has been traditionally used as anti-ageing and health promotive tonic. The purpose of this study was to investigate its nephroprotective effect and mechanism via antioxidant and antiapoptotic potential in Streptozotocin-induced diabetic nephropathy (DN) in rats. Methods: The chemical composition of aqueous extract of Pueraria tuberosa (PTY-2r) was analyzed by gas chromatography-mass spectrometry (GC-MS). Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) (55 mg/kg body weight) in rats. After 60 days, the rats were randomly divided into 3 groups (n = 6/each group), namely DN control (DN) group-2, DN rats treated with PTY-2r at the dose of 50 mg/100 g, group-3 and 100 mg/100 g, group-4 p.o. for 20 days. The normal rats were chosen as a normal control (NC) group-1. PTY-2r was orally given to the rats for 20 days. Reactive oxygen species (ROS), lipid peroxidation (LPO) and the activity of ROS-scavenging enzymes - superoxide dismutase (SOD), catalase (CAT) & glutathione peroxidase (GPx) were determined in the kidney tissue of DN rats. The expression of apoptosis-related proteins was measured by immunofluorescence. Results: GC-MS analysis of PTY-2r indicated the presence of 37 compounds among them 5-Hydroxymethylfurfural (17.80%), 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one (17.03%), n-Hexadecanoic acid (5.18%) and 9-Octadecenoic acid (Z) - (6.69%) were found in the higher amount. A significant increase in ROS and LPO was observed along with the decreased activity of antioxidant enzymes, responsible for oxidative stress in the kidney of DN rats. Since, high oxidative stress induces apoptosis in target cells, as shown by significantly decreased expression of Bcl-2 along with increased expression of Bax, active Caspase-3 & cleaved PARP-1 in DN control rats, suggesting apoptosis. The PTY-2r treatment significantly raised the activity of antioxidant enzymes, suppressed oxidative stress and apoptosis thus, prevented urinary albumin excretion in a dose-dependent manner. Conclusions: The findings suggest that PTY-2r exerted the nephroprotective potential against STZ induced DN rats via suppressing oxidative stress and apoptosis due to the presence of different bioactive compounds. © 2018 The Author(s).
Effect of extract of Pueraria tuberosa on expression of hypoxia inducible factor-1α and vascular endothelial growth factor in kidney of diabetic rats
(Elsevier Masson SAS, 2017) Rashmi Shukla; Nidhi Pandey; Somanshu Banerjee; Yamini B. Tripathi
Backgrounds Kidney hypoxia represents a unifying mechanism in the pathogenesis of diabetic nephropathy. Hypoxia-induced factor (HIF)-1α mediates the metabolic responses of renal hypoxia by modulating the expression of VEGF. In the present study, we investigated the effect of Pueraria tuberosa extract (PTY-2r) on the expression of HIF-1α, VEGF and nephrin in streptozotocin (STZ) induced diabetic nephropathy (DN). Methods The model of diabetic nephropathy (DN) was produced by intraperitoneal injection of 55 mg/kg of STZ and maintained for 60 days. These DN-rats were randomly divided into three groups, i.e., DN, DN + PTY-2r (100 mg/100 g), and DN + PTY-2r (50 mg/100 g). A normal control (NC) group was administrated with drug vehicle. Expression of HIF-1α, VEGF and nephrin were evaluated in the renal tissue. Results Blood glucose, urine protein, serum creatinine, and urea, level were significantly raised along with decreased creatinine clearance in DN rats. Immunofluorescence and Western blot analysis showed significantly increased expression of HIF-1α & VEGF and decreased expression of nephrin in DN control rats. The PTY-2r treatment significantly reversed these changes in a dose-dependent manner. Correlation analysis showed that the expression of VEGF was positively correlated with that of HIF-1α and negatively correlated with nephrin. Conclusions The PTY-2r can improve the chronic hyperglycemic condition induced kidney damage, and may delay the development of diabetic nephropathy by inhibiting the expression of HIF-1α and VEGF, thereby restoring the expression of nephrin. © 2017
Engineered Cellular Uptake and Controlled Drug Delivery Using Two Dimensional Nanoparticle and Polymer for Cancer Treatment
(American Chemical Society, 2018) Sudipta Senapati; Rashmi Shukla; Yamini Bhusan Tripathi; Arun Kumar Mahanta; Dipak Rana; Pralay Maiti
Two major problems in chemotherapy, poor bioavailability of hydrophobic anticancer drug and its adverse side effects causing nausea, are taken into account by developing a sustained drug release vehicle along with enhanced bioavailability using two-dimensional layered double hydroxides (LDHs) with appropriate surface charge and its subsequent embedment in polymer matrix. A model hydrophobic anticancer drug, raloxifene hydrochloride (RH), is intercalated into a series of zinc iron LDHs with varying anion charge densities using an ion exchange technique. To achieve significant sustained delivery, drug-intercalated LDH is embedded in poly(ϵ-caprolactone) (PCL) matrix to develop intravenous administration and to improve the therapeutic index of the drug. The cause of sustained release is visualized from the strong interaction between LDH and drug, as measured through spectroscopic techniques, like X-ray photoelectron spectroscopy, infrared, UV-visible spectroscopy, and thermal measurement (depression of melting temperature and considerable reduction in heat of fusion), using differential scanning calorimeter, followed by delayed diffusion of drug from polymer matrix. Interestingly, polymer nanohybrid exhibits long-term and excellent in vitro antitumor efficacy as opposed to pure drug or drug-intercalated LDH or only drug embedded PCL (conventional drug delivery vehicle) as evident from cell viability and cell adhesion experiments prompting a model depicting greater killing efficiency (cellular uptake) of the delivery vehicle (polymer nanohybrid) controlled by its better cell adhesion as noticed through cellular uptake after tagging of fluorescence rhodamine B separately to drug and LDH. In vivo studies also confirm the sustained release of drug in the bloodstream of albino rats using polymer nanohybrid (novel drug delivery vehicle) along with a healthy liver vis-à-vis burst release using pure drug/drug-intercalated LDHs with considerable damaged liver. © 2018 American Chemical Society.
Neuroprotective effect of Reinwardtia indica against scopolamine induced memory-impairment in rat by attenuating oxidative stress
(Springer, 2020) Prabhat Upadhyay; Rashmi Shukla; Kavindra Nath Tiwari; G.P. Dubey; Sunil Kumar Mishra
Reinwardtia indica belongs to Linaceae family and used as a folk medicine in Asian countries. Traditionally, it has been used in the treatment of paralysis and anti-microbial in wound healing, etc. The current study was undertaken in order to investigate the antioxidant and memory protective effect of the alcoholic (99.90%) (AERI) and hydro-alcoholic (70:30) leaves extract (HAERI) of Reinwardtia indica, against scopolamine-induced memory impairment in animals and also tried to determine the possible mechanism of action. In addition, phytochemical profiling of alcoholic leaves extract was also conducted through gas chromatography-mass spectrometry (GC-MS/MS). Rats were pretreated with AERI, HAERI (dose 250 and 500 mg/kg) and Donepezil (standard drug) along with scopolamine (1 mg/kg) for a period of 14 days followed by different test like elevated plus maze, passive avoidance, and Morris water maze to assess learning and memory ability. Acetylcholine levels, acetylcholinesterase (AChE), antioxidant enzymes (SOD, CAT & GSH), histopathology of the brain and biochemical test were also performed at the end of the treatment period. The scopolamine treatment resulted in learning and memory deficits which were partially and significantly ameliorated by the AERI at higher dose among other doses of extracts. The AERI at higher dose also counteracted the scopolamine-induced decrease in acetylcholine levels, increase in AChE activity, and decrease in antioxidant enzymes activities. No significant changes observed in the biochemical estimation of all dose of extracts. Histology of brain tissue showed the marked cellular changes in only scopolamine treated group while the standard, AERI and HAERI treated group were showing less damage at hippocampus region of the brain. The phytochemicals found after chemical profiling through GC-MS also supported the activity because of the presence of chemicals already reported for the neuroprotective, memory-enhancing and antioxidant activity, etc. The results demonstrated that the ability of the AERI at higher dose among all doses of extracts has more potential to revert the scopolamine-induced learning and memory deficits in rats by attenuating the decreased level of acetylcholine and antioxidant enzymes. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.
Pueraria tuberosa extract inhibits iNOS and IL-6 through suppression of PKC-α and NF-kB pathway in diabetes-induced nephropathy
(Blackwell Publishing Ltd, 2018) Rashmi Shukla; Somanshu Banerjee; Yamini B. Tripathi
Objectives: Inflammation plays an important role in the pathogenesis of diabetic nephropathy (DN). The aim of this study was to explore the anti-inflammatory role of PTY-2r (extracted from Pueraria tuberosa), on streptozotocin (STZ)-induced DN rats. Methods: Diabetes was induced by intraperitoneal injection of STZ (55mg/kg) in rats. After 60 days, the rats were randomly divided into three groups (n = 6/each group), namely DN control group 2, DN rats treated with PTY-2r at dose of 100 mg/100 g, group 3 and 50 mg/100 g, group 4, p.o for 20 days. The normal rats were chosen as a normal control (NC) group 1. Key findings: In DN rats, the expression of iNOS and inflammatory cytokines (IL-6 and TNF-α) was significantly increased. Raised expression of PKC-α was also found. As NF-kB is the main transcription factor for the inflammatory response-mediated progression of DN, variation in NF-kB expression and its activated phosphorylated derivative (pNF-kB) were also evaluated and increase in expression was obtained in the kidney of DN rats. PTY-2r treatment significantly reversed these changes in dose-dependent manner. Conclusions: This study suggested that the nephroprotective effect of PTY-2r is possibly due to downregulation of PKC-α and NF-kB pathway and normalizing the expression of inflammatory cytokines and iNOS in the kidney of DN rats. © 2018 Royal Pharmaceutical Society
Toxicity assessment of the alcoholic leaves extract of reinwardtia indica
(Faculdade de Ciencias Farmaceuticas (Biblioteca), 2019) Prabhat Upadhyay; Rashmi Shukla; Kavindra Nath Tiwari; G.P. Dubey; Sunil Kumar Mishra
The present study aimed to evaluate the safety of the alcoholic leaves extract of Reinwardtia indica in Charles foster rats through an acute and sub-acute oral administration.For assessment of acute oral toxicity test, ratswere orally treated with single dose of the alcoholic leaves extract of Reinwardtia indica at the doses of 50, 250, 500, 1000 2000 and 5000 mg/kg. In sub-acute toxicity study, using the OECD guidelines no. 407, the extract was administered at the doses of 50, 250, 500, 1000, 2000 mg/kg/day for 28 consecutive days and at the dose of 2000 mg/kg satellite group also used for 6 weeks.In acute toxicity above mentioned doses neither showed mortality nor exterior signs of toxicity. In sub-acute, study no significant changes found in haematological and biochemical level ofthe treated rat after 14 days and 28 days in comparison to control. The histopathology of rat brain, kidney, liver, and heart also showed the no cellular changes after extract treated rat.The alcoholic leaves extract of Reinwardtia indica was found non-toxic in single drug dose administration up to 5000 mg/kg (acute study) and in sub-acute administration up to 2000 mg/kg. © 2019, Faculdade de Ciencias Farmaceuticas (Biblioteca). All rights reserved.