Chronic toxicity studies of gandhaka rasayana - A herbo-mineral preparation used in Ayurvedic practice.

BACKGROUND: Gandhaka rasayana (GR) is an important component of many Ayurvedic formulations besides being used as a standalone therapy. However, literature review revealed a chronic toxicity studies with longer duration. OBJECTIVES: To delineate the safety profile of GR for 180 days administration in rats. MATERIALS AND METHODS: Wistar albino rats of both sexes weighing 150 ± 10 g body weight in groups of 20 (10 male and 10 female) for each of the three GR dose levels i.e., 0.54 g, 1.08 g, and 5.4 g/kg were employed. Carboxyl methyl cellulose was administered to the control group in equal volume. Toxicity was assessed based on the changes observed, compared to control, in body weight gain, food and water consumption, organ weight and histopathology, clinical biochemistry, and hematological parameters as per AYUSH guidelines. RESULTS: GR repeated dose administration caused significant changes in body weight gain, organ ponderal changes, few hematologic and biochemical parameters. Male rats administered with GR at 1.08 g/kg dose showed a significant decrease in the MCV and MCH compared to control, whereas female rat's administred with 1.08 g/kg and 0.54 g/kg dose showed a significant increase in the MCV and MCH. GR administered at 0.54 g/kg showed a significant increase in the serum glucose level in male rats, whereas female rats showed a significant elevation in the cholesterol level. GR at 0.54 g/kg and 5.4 g/kg showed a significant elevation in the serum SGPT level in male rats. These changes were not observed in female rats. Histological examination revealed mild pathological changes in organs like kidney, liver, spleen and jejunum. CONCLUSION: The data generated shows that GR is safe and does not have any toxicity potential at the doses used in therapeutics. Some of the changes observed were at higher dose levels which is not likely to be used clinically.

Effect of Helicanthes elasticus (Desv.) Danser extracts on immune profile of Wistar albino rats.

Helicanthes elasticus (Desv.) Danser is a common type of mistletoes of Indian origin. In Indian traditional and folklore medicines the plant is claimed to possess a range of medicinal values such as immunomodulator, anti-diabetic and anti-microbial properties. However, there is no experimental proof for its therapeutic claim. The aqueous and alcoholic extracts of H. elastica were evaluated for its immuno-modulatory effect on antibody formation against sheep red blood cells and on cell mediated immunity of immunological paw edema model. Ethanolic and aqueous extracts have shown dose dependent elevation in the antibody titer value in comparison to control group at 14th and 21st day of sensitization (**p < 0.01). There is a mild to moderate elevation were observed in the immunological paw edema at highest dose (400 mg/kg) during 21st day after sensitization. The histopathological observation shows that there is an increase in the white pulp of spleen and increased cellularity and formation of distinct germinal cells in lymph node. H. elasticus extracts possess marked antibody formation propensity without significant modification on cell mediated immunity.

Possible Clues for Brain Energy Translation via Endolysosomal Trafficking of APP-CTFs in Alzheimer's Disease.

Vascular dysfunctions, hypometabolism, and insulin resistance are high and early risk factors for Alzheimer's disease (AD), a leading neurological disease associated with memory decline and cognitive dysfunctions. Early defects in glucose transporters and glycolysis occur during the course of AD progression. Hypometabolism begins well before the onset of early AD symptoms; this timing implicates the vulnerability of hypometabolic brain regions to beta-secretase 1 (BACE-1) upregulation, oxidative stress, inflammation, synaptic failure, and cell death. Despite the fact that ketone bodies, astrocyte-neuron lactate shuttle, pentose phosphate pathway (PPP), and glycogenolysis compensate to provide energy to the starving AD brain, a considerable energy crisis still persists and increases during disease progression. Studies that track brain energy metabolism in humans, animal models of AD, and in vitro studies reveal striking upregulation of beta-amyloid precursor protein (ß-APP) and carboxy-terminal fragments (CTFs). Currently, the precise role of CTFs is unclear, but evidence supports increased endosomal-lysosomal trafficking of ß-APP and CTFs through autophagy through a vague mechanism. While intracellular accumulation of Aß is attributed as both the cause and consequence of a defective endolysosomal-autophagic system, much remains to be explored about the other ß-APP cleavage products. Many recent works report altered amino acid catabolism and expression of several urea cycle enzymes in AD brains, but the precise cause for this dysregulation is not fully explained. In this paper, we try to connect the role of CTFs in the energy translation process in AD brain based on recent findings.

Pluchea lanceolata protects hippocampal neurons from endothelin-1 induced ischemic injury to ameliorate cognitive deficits.

Ischemic brain injury is one of the leading causes of death and disability, where lack of disease modifying treatment strategies make us rely on symptomatic relief. Treatment principles from traditional systems of medicine may fill this gap and its validation in modern medicine perspective is important to bring them to mainstream. Here, we evaluated the neuroprotective efficacy of Ayurvedic medicinal herb Pluchea lanceolata in treating ischemic hippocampal injury. Focal hippocampal ischemia was modeled in Wistar rats through stereotaxic intrahippocampal injection of endothelin-1 (ET-1). Post-surgery, hydroalcoholic extract of the rhizome of Pluchea lanceolata (HAPL) was administered orally, once in a day for 14 consecutive days to ischemic rats. There were two treatment groups based on the HAPL dosage; HAPL200 (200 mg/kg body weight) and HAPL400 (400 mg/kg body weight). Comparisons were made with the ET-1 ischemic rats which received only the vehicle, and the normal surgical control. Ischemic hippocampal injury led to severe cognitive deficits as evaluated by Morris water maze and open field test, along with locomotory dysfunction noted in actophotometer test. HAPL treatment significantly attenuated these behavioural deficits in a dose dependent manner. Loss of pyramidal cells and degenerative phenotype of shrunken hyperdensed soma with pyknotic nuclei in CA1 and CA3 hippocampal neurons in ischemia were reversed after HAPL treatment. We provide first evidence for loss of dendritic architecture in ET-1 induced focal ischemic hippocampal injury using Golgi impregnation, where HAPL could salvage the dendritic branching and intersections. Intriguingly, it enhanced the dentritic arborization beyond what is noted in normal rats. Ability of HAPL to reverse oxidative stress, especially through maintaining glutathione peroxidase levels and lipid peroxidation in ischemic condition evidences that it may exert neuroprotection through its antioxidant properties. Thus, Pluchea lanceolata and its constituents provide potential alternative/adjuvant treatment strategy for ischemic hippocampal stroke.

Multiple pharmacological activities of Caesalpinia crista against aluminium-induced neurodegeneration in rats: Relevance for Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia and mainly affects cognitive function of the aged populations. Aluminium, a neurotoxic metal, has been suggested as a contributing factor of AD. Caesalpinia crista is a medicinal plant known for its anti-microbial, anti-inflammatory and anti-oxidant properties. The present study was conducted in order to evaluate the neuroprotective effects of methanolic extracts of C. crista (MECC) on aluminium-induced neurodegeneration in rats. Co-administration with MECC significantly and dose dependently ameliorated the aluminium-dependent cognitive impairment, AChE hyperactivity and oxidative stress in the hippocampus and in the frontal cortex of rat brain. Moreover, MECC reduced the neuronal injury induced by aluminium as shown by the diminution of neuron loss and pyknosis in the CA1 and CA3 regions of the hippocampus. From this study, it is inferred that MECC protect against aluminium-induced behavioral alterations, cognitive function, oxidative stress and neuroinflammation in vivo. Therefore, this plant may serve as a source of natural products having multiple functions and could be utilized as an anti-AD preparation.

Protective Effect of Pluchea lanceolata against Aluminum Chloride-induced Neurotoxicity in Swiss Albino Mice.

BACKGROUND: Aluminum chloride (AlCl3) is a known potent environmental neurotoxin causing progressive neurodegenerative changes in the brain. The herb Pluchea lanceolata is commonly known as "Rasana" and used as a nerve tonic in neuroinflammatory conditions in Indian system of medicine. OBJECTIVE: To evaluate the neuroprotective activity of hydroalcoholic extract of P. lanceolata in chronic AlCl3-induced neurotoxicity in Swiss albino mice. MATERIALS AND METHODS: Albino mice were categorized into four different groups; Group 1served as vehicle control, Group 2 mice were administered with AlCl3, 40 mg/kg body weight by intraperitoneal route for 45 consecutive days. Groups 3 and 4 mice were administered with AlCl3, 40 mg/kg body weight intraperitoneal for 45 consecutive days along with hydroalcoholic extract of P. lanceolata at 200 and 400 mg/kg body weight. RESULTS: Chronic administration of AlCl3 resulted in behavioral deficits, triggered lipid peroxidation, increased acetylcholinesterase (AChE) activity, and histological alterations. Co-administration of hydroalcoholic extract of P. lanceolata attenuated many of the AlCl3-induced alterations such as behavioral, lipid peroxidation, AChE, and histological changes of brain tissue. CONCLUSION: The results of the present study have demonstrated the protective role of hydroalcoholic extract of P. lanceolata against AlCl3-induced neurotoxicity in Swiss albino mice. The neuroprotective efficacy of P. lanceolata can help reduce the symptoms caused by toxic protein aggregates in several degenerative diseases. SUMMARY: The hydro alcoholic extract of Pluchea lanceolata showed neuroprotective activity in albino mice against AlCl3 toxicityThe benefits of Pluchea lanceolata against AlCl3 toxicity includes reduced lipid peroxidation and acetylcholine esterase activity with improved behavioral functionsThe hydro alcoholic extract of Pluchea lanceolata rendered protection against AlCl3 in forebrain, midbrain, cerebellum and hippocampusTherefore Pluchea lanceolata holds pharmacological potentials for treating diseases associated with neuronal toxicity. Abbreviations used: HAPL: Hydro alcoholic extract of Pluchea lanceolata; CAT: Catalase; GSH-Px: Glutathione peroxidase; SOD: Superoxide dismutase; TBARS: Thio-barbituric acid reactive substances; MDA: Malondialdehyde; AChE: Acetylcholine esterase; AOT: Acute oral toxicity; CNS: Central nervous system; H2O2: Hydrogen peroxide; ML: molecular layer; GL: granular layer; MC: microcytic changes; BV: blood vessels; DG: dentate gyrus; PC: pyramidal cells; LD: Lethal dose; ANOVA: Analysis of variance; SEM: Standard error of mean; PCL: Pyramidal cell layer; OCL: Outer granular layer; BV: blood vessels; PM: Pia mater.

In-vivo study of tissue reaction to Crotalaria pallida and Sansevieria roxburghiana fibers.

BACKGROUND: A suture material producing least tissue reaction is considered as ideal. Other characteristics like tensile strength, capacity to sustain sterilization process enhance its acceptability. In the present situation there is a need to reascertain the relevance and utility of these materials. Among the suture materials mentioned by Sushrutacharya, Moorva (Sansevieria roxburghiana) and Shana (Crotalaria pallida) have been showed insignificant tissue reaction in operated cases of inguinal hernia. An experimental study to confirm the extent of tissue reaction in deeper planes is needed before extending the use of materials in the deep tissues. OBJECTIVE: The objective of the study was to analyze deep tissue reaction and tensile strengths of plant fibres extracted from Crotalaria pallida and Sansevieria roxburghiana. MATERIALS AND METHODS: The study was conducted on 18 albino rats, 3 groups of 6 rats each for a period of 21 days inserting the suture materials in deeper tissue, studying histopathology changes of the deeper connective tissues, hydroxyproline content and blood parameters on 7th, 14th, 21st days of the study. The tensile strength of the two materials was also assessed on 7th day in three different conditions. Statistical analysis was carried out using paired and unpaired t tests. RESULTS: S. roxburghiana had least tissue reaction. C. pallida showed greater tensile strength in comparison to Moorva. CONCLUSION: C. pallida can be used for deep tissue approximation because of its moderate tissue reaction and tensile strength, successive increase in hydroxyproline content and its capacity to sustain sterilization.