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Purpose: Alzheimer’s is a disease affecting mostly the Older population leading to the deterioration of cognitive capabilities. The protective effect of Caffeic acid in Colchicineinduced dementia was evaluated in the current study. Materials and Methods: Colchicinewas administered intracerebroventricularly (ICV) to the lateral ventricle of the brain (at the coordinates 0.8 mm posterior to bregma, 1.8 mm lateral to the sagittal suture, 3.6 mm below the cortical surface) using robotic stereotaxic apparatus that results in Alzheimer’s type sporadic dementia. Caffeic acid at the dose of 50 mg/kg p.o, was administered daily for 25 days starting four days before the colchicine injection and evaluated for its neuroprotective activity. The spatial memory of animals was evaluated using Morris water maze followed by biochemical estimations of acetylcholinesterase and antioxidant markers in the hippocampal and frontal cortex region of the brain. Results: Intracerebroventricular injection of colchicine in rat brain resulted in decreased cognitive abilities as evident in escape latency and average speed of the retention trial. Significant changes in the escape latency were noted in Caffeic acid-treated group. The level of acetylcholinesterase and antioxidant markers like glutathione, catalase, lipid peroxidation, superoxide dismutase were significantly changed in the hippocampal region of the rats but not in the frontal cortex region in the caffeic acid treatment groups. Conclusion: The current study provides evidence for the neuroprotective and antioxidative potential of caffeic acid in intracerebroventricularly injected Colchicine-induced sporadic model of AD.

Alzheimer disease (AD) is the most common, irreversible and progressive form of dementia for which the exact pathology and cause are still not clear. At present, we are only confined to symptomatic treatment, and the lack of disease-modifying therapeutics is worrisome. Alteration of Wnt signaling has been linked to metabolic diseases as well as AD. The crosstalk between Canonical Wnt signaling and insulin signaling pathway has been widely studied and accepted from several clinical and preclinical studies that have proven the beneficial effect of antidiabetic medications in the case of memory and cognition loss. This structure-based in silico study was focused on exploring the link between the currently available FDA approved antidiabetic drugs and the Wnt signaling pathway. The library of antidiabetics was obtained from drug bank and was screened for their binding affinity with protein (PDB ID: 3S2K) LRP6, a coreceptor of the Wnt signaling pathway using GLIDE module of Schrodinger. The top molecules, with higher docking score, binding energy and stable interactions, were subjected to energy-based calculation using MMGBSA, followed by a molecular dynamics-based simulation study. Drugs of class α-glucosidase inhibitors and peroxisome proliferator-activated receptors (PPARs) agonists were found to have a strong affinity towards LRP6 proteins, highlighting the possibility of the modulation of Wnt signaling by antidiabetics as one of the possible mechanisms for use in AD. However, further experimental based in vitro and in vivo studies are warranted for verification and support.Communicated by Ramaswamy H. Sarma.

Human immunodeficiency virus-1 (HIV-1) infection remains to be one of the major threats throughout the world. Many researchers are working in this area to find a cure for HIV-1. The group of the FDA approved drugs which are currently used against HIV-1 in the clinical practice include nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), integrase inhibitors (InIs), and protease inhibitors (PIs). Fixed dose combinations (FDCs) of these drugs are available and are used as per the anti-retroviral therapy (ART) guidelines. Despite these, unfortunately, there is no cure for HIV1 infection to date. The present review is focused upon describing the importance of a post-transcriptional regulatory protein “Rev”, responsible for latent HIV-1 infection as a possible, and promising therapeutic target against HIV-1.

Nanotechnology has created a revolutionary change for the past two decades, with significantly improved precision-based nanomedicine with improved targeted cellular bioavailability, potency, and reduced toxicity in the field of unmet clinical needs. The amalgamation of therapeutics and diagnostics into a single agent of nanoscale range termed as nanotheranostics technique has improved the area of diagnosis and individualized therapy. With this advancement, there is an urgent need for regulatory bodies to understand the science involved and thereby regulate these products to protect public health. The currently available testing approaches are limited and not enough to evaluate nanotoxicology for the clinical translation of the developed nanoscale medicinal products. Several specific techniques are under development for nanomedicines. Currently, there are no specific regulations regarding nanocarriers for drug delivery. There is a need for a dedicated protocol for the evaluation of nanoformulations with concern to the activity, safety, and toxicity of the active molecules as well as the nanocarrier.

Background: Infants of the diabetic mother are known to have reduced bone mineral content and hypocalcemia. Earlier, it has been shown that petroleum ether extract of Cissus quadrangularis (PECQ) can enhance the fetal skeletal ossification in normal rats. The present study was designed to evaluate the effect of ECQ on skeletal growth in the neonatal rats of streptozotocin-induced diabetic rats.Methods: After confirmation of diabetes, the diabetic and non-diabetic female Wistar rats were kept for mating with healthy male rats. After positive vaginal smear test, the pregnant rats were divided into three groups; the normal (non-diabetic) control (NC), diabetic control (DC), and diabetic+CQ (D+CQ) groups. The rats in the D+CQ group were given PECQ (500 mg/kg B.Wt), whereas animals in NC and DC groups were given 0.5% carboxy methyl cellulose, throughout the gestational period. Femur from the 1 week old neonatal rats from each group was collected randomly and subjected to histological analysis. Results: Thickness of trabecular bone and periosteum was significantly reduced in the neonates of DC rats compared with the neonates of NC group. Pretreatment with PECQ significantly improved the thickness of trabecular bone and periosteum compared with neonatal rats of DC group. No significant differences were observed in the medullary cavity width of femur between the groups. Conclusion: Data from the present study suggest that the PECQ can effectively attenuate the diabetes-induced reduction in the early skeletal growth. However, further research is warranted to evaluate the exact mechanism of action of phytochemical constituents of PECQ that can cross the placental barrier.

Background: Delayed fetal skeletal ossification is one of the known complications of maternal diabetes. Objective: The present study was designed to evaluate the protective role of petroleum ether extract of Cissus quadrangularis (PECQ) on diabetes-induced delayed fetal skeletal ossification. Materials and Methods : Female Wistar rats were rendered diabetic with streptozotocin (STZ, 40 mg/kg, intraperitonial) before mating. After confirmation of pregnancy, the pregnant rats were divided into three groups: normal control group, diabetic control group, and diabetic + CQ group. The diabetic + CQ group pregnant rats were treated with PECQ (500 mg/kg body weight) throughout their gestation period. Immediately after delivery, pups were collected from all three groups and processed for alizarin red S-alcian blue staining in order to examine the pattern of skeletal ossification. Results : Fewer ossification centers and decreased extent of ossification of forelimb and hindlimb bones were observed in the neonatal pups of diabetic control group as compared to those in the normal control group. PECQ pretreatment significantly restored the ossification centers and improved the extent of ossification of forelimb and hindlimb bones in the neonatal pups of diabetic + CQ group as compared to those in the diabetic control group. Conclusions : The results suggested that PECQ treatment is effective against diabetes-induced delayed fetal skeletal ossification. However, further studies on the isolation and characterization of active constituents of PECQ, which can cross the placental barrier and are responsible for the bone anabolic activity are warranted.