Chitosan-based nanofibrous scaffolds for biomedical and pharmaceutical applications: A comprehensive review.

Nowadays, there is a wide range of deficiencies in treatment of diseases. These limitations are correlated with the inefficient ability of current modalities in the prognosis, diagnosis, and treatment of diseases. Therefore, there is a fundamental need for the development of novel approaches to overcome the mentioned restrictions. Chitosan (CS) nanoparticles, with remarkable physicochemical and mechanical properties, are FDA-approved biomaterials with potential biomedical aspects, like serum stability, biocompatibility, biodegradability, mucoadhesivity, non-immunogenicity, anti-inflammatory, desirable pharmacokinetics and pharmacodynamics, etc. CS-based materials are mentioned as ideal bioactive materials for fabricating nanofibrous scaffolds. Sustained and controlled drug release and in situ gelation are other potential advantages of these scaffolds. This review highlights the latest advances in the fabrication of innovative CS-based nanofibrous scaffolds as potential bioactive materials in regenerative medicine and drug delivery systems, with an outlook on their future applications.

Neurotrophin mimetics and tropomyosin kinase receptors: a futuristic pharmacological tool for Parkinson's.

Parkinson's disease is a complex age-related progressive dopaminergic neurodegenerative disease consistently viewed as a disorder of movement and is characterized by its cardinal motor symptoms. While the motor symptoms and its clinical manifestations are attributed to the nigral dopaminergic neuronal death and basal ganglia dysfunction, studies have subsequently proven that the non-dopaminergic neurons in various brain regions are also additionally involved with the disease progression. Thus, it is now well accepted that the involvement of various neurotransmitters and other ligands accounts for the non-motor symptoms (NMS) associated with the Parkinson's disease. Consequently, this has demonstrated to possess remarkable clinical concerns to the patients in terms of various disability, such impaired to compromised quality of life and increased risk of morbidity and mortality. Currently, available pharmacological, non-pharmacological, and surgical therapeutic strategies neither prevent, arrest, nor reverse the nigral dopaminergic neurodegeneration. Thus, there is an imminent medical necessity to increase patient's quality of life and survival, which in turn decreases the incidence and prevalence of the NMS. The current research article reviews the potential direct involvement of neurotrophin and its mimetics to target and modulate neurotrophin-mediated signal transduction pathways to enlighten a new and novel therapeutic strategy along with the pre-existing treatments for Parkinson's disease and other neurological/neurodegenerative disorders which are associated with the downregulation of neurotrophins.

Chemistry, Biosynthesis and Pharmacology of Sarsasapogenin: A Potential Natural Steroid Molecule for New Drug Design, Development and Therapy.

Sarsasapogenin is a natural steroidal sapogenin molecule obtained mainly from Anemarrhena asphodeloides Bunge. Among the various phytosteroids present, sarsasapogenin has emerged as a promising molecule due to the fact of its diverse pharmacological activities. In this review, the chemistry, biosynthesis and pharmacological potentials of sarsasapogenin are summarised. Between 1996 and the present, the relevant literature regarding sarsasapogenin was obtained from scientific databases including PubMed, ScienceDirect, Scopus, and Google Scholar. Overall, sarsasapogenin is a potent molecule with anti-inflammatory, anticancer, antidiabetic, anti-osteoclastogenic and neuroprotective activities. It is also a potential molecule in the treatment for precocious puberty. This review also discusses the metabolism, pharmacokinetics and possible structural modifications as well as obstacles and opportunities for sarsasapogenin to become a drug molecule in the near future. More comprehensive preclinical studies, clinical trials, drug delivery, formulations of effective doses in pharmacokinetics studies, evaluation of adverse effects and potential synergistic effects with other drugs need to be thoroughly investigated to make sarsasapogenin a potential molecule for future drug development.

Neuroprotective role of Diosgenin, a NGF stimulator, against Aß (1-42) induced neurotoxicity in animal model of Alzheimer's disease.

Diosgenin is a neurosteroid derived from the plants and has been previously reported for its numerous health beneficial properties, such as anti-arrhythmic, hypolipidemic, and antiproliferative effects. Although several studies conducted earlier suggested cognition enhancement actions of diosgenin against neurodegenerative disorders, but the molecular mechanisms underlying are not clearly understood. In the present study, we investigated the neuroprotective effect of diosgenin in the Wistar rats that received an intracerebroventricular injection of Amyloid-ß (1-42) peptides, representing a rodent model of Alzheimer's disease (AD). Animals were treated with 100 and 200 mg/kg/p.o of diosgenin for 28 days, followed by Amyloid-ß (1-42) peptides infusion. Animals were assessed for the spatial learning and memory by using radial arm maze and passive avoidance task. Subsequently, animals were euthanized and brains were collected for biochemical estimations and histopathological studies. Our results revealed that, diosgenin administration dose dependently improved the spatial learning and memory and protected the animals from Amyloid-ß (1-42) peptides induced disrupted cognitive functions. Further, biochemical analysis showed that diosgenin successfully attenuated Amyloid-ß (1-42) mediated plaque load, oxidative stress, neuroinflammation and elevated acetylcholinesterase activity. In addition, histopathological evaluation also supported neuroprotective effects of diosgenin in hippocampus of rat brain when assessed using hematoxylin-eosin and Cresyl Violet staining. Thus, the aforementioned effects suggested protective action of diosgenin against Aß (1-42) induced neuronal damage and thereby can serve as a potential therapeutic candidate for AD.

Chandamarutha Chenduram, an Indian traditional Siddha preparation attenuated the neuronal degeneration in ischemic mice through ameliorating cytokines and oxy-radicals mediated EAAT-2 dysfunction.

ETHNOPHARMACOLOGICAL RELEVANCE: Chandamarutha Chenduram (CC), an Indian traditional Siddha preparation officially recorded in the Siddha formulary of India and its composition are widely used in the Siddha practice of neurological disorders like stroke/paralysis in India. However, the scientific validation and mechanistic evidence is lacking and yet to be elucidated. AIM OF THE STUDY: To establish the scientific evidences and to explore the possible neuroprotective mechanism of CC in cerebral ischemia. MATERIALS AND METHODS: Chemical standardization of the CC was performed using atomic absorption spectroscopy and gravimetric analysis. Acute toxicity study for CC in mice was performed in accordance with OECD 423 guidelines. CC (5 mg/kg) and CC (10 mg/kg) were investigated in bilateral common carotid occlusion (BCCAo) model in mice. After, behavioral assessments, the brain samples were collected and the hippocampus region was micro-dissected for neurotransmitter, neurobiochemicals and inflammatory cytokines estimation. The excitatory amino acid transporter-2 (EAAT-2) expressions was analyzed by RT-PCR to understand the possible molecular mechanism. In addition, hematoxylin and eosin staining of CA1 hippocampal brain region was performed to support the neuroprotective effect of CC in ischemic condition. RESULTS: Chemical standardization analysis showed that CC has acceptable range of mercury (0.82 ppm) and elemental sulphur (11% w/w). Also, other heavy metal limits were found to be less or not detectable. Toxicity study also evidenced the safety profile of CC. CC has significantly reversed the behavioral dysfunctions (p < 0.001) in global ischemic mice. Treatment with CC has attenuated the excitatory neurotransmitter glutamate, lipid peroxide, nitric oxide, cytokines (IL-1ß, TNF-α) (p < 0.001) and increased the antioxidant enzymes (SOD, CAT, GSH) and EAAT-2 expression level (p < 0.001) in ischemic brain. The hematoxylin and eosin staining in CA1 region of hippocampus also evidence the neuroprotective effect exhibited by CC. CONCLUSIONS: Treatment with CC has exhibited dose dependent effect and CC10 has shown significant protective effect in comparison to CC5 in most of the parameters studied. CC prevented further degeneration of neurons in cerebral ischemic mice through ameliorating inflammatory cytokines and oxy-radicals mediated EAAT-2 dysfunction and subsequent excitotoxicity in neurons.

Towards next-generation personalization of tacrolimus treatment: a review on advanced diagnostic and therapeutic approaches.

The benefit of personalized medicine is that it allows the customization of drug therapy - maximizing efficacy while avoiding side effects. Genetic polymorphisms are one of the major contributors to interindividual variability. Currently, the only gold standard for applying personalized medicine is dose titration. Because of technological advancements, converting genotypic data into an optimum dose has become easier than in earlier years. However, for many medications, determining a personalized dose may be difficult, leading to a trial-and-error method. On the other hand, the technologically oriented pharmaceutical industry has a plethora of smart drug delivery methods that are underutilized in customized medicine. This article elaborates the genetic polymorphisms of tacrolimus as case study, and extensively covers the diagnostic and therapeutic technologies which aid in the delivery of personalized tacrolimus treatment for better clinical outcomes, thereby providing a new strategy for implementing personalized medicine.

Optimal Dosing of Lasmiditan in the Management of Acute Migraine Attack: A Systematic Review and Meta-analysis.

BACKGROUND: The current target of migraine treatment is focused on Triptans. Lasmiditan, a non-vasoconstrictive and highly selective 5HT1F receptor agonist is a novel therapeutic discovery for migraine for patients with cardiovascular (CV) risk factors or stable cardiovascular diseases and who fail to respond to the existing treatment. OBJECTIVE: To identify an optimal dosing of Lasmiditan 100 mg versus 200 mg for the treatment of acute migraine attacks in adult patients with cardiovascular risk factors. METHODS: Systematic searches were run in databases such as Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Google scholar, and PUBMED. Out of 83 study records identified, two studies were included for quantitative analysis. RESULTS: There was a significant headache pain freedom at 2 h [Odds Ratio (OR): 0.77; 95% Confidence interval (CI): 0.64-0.92] and sustained pain freedom at 24 h (OR): 0.75; 95% CI: 0.61-0.93] in patients taking Lasmiditan 200 mg compared to those taking Lasmiditan 100 mg. The results were statistically insignificant for parameters like most bothersome symptoms (MBS) free at 2 h, headache relief at 2 h, disability level at 2 h, and global impression of change at 2 h. A combined analysis of these parameters showed a remarkable difference between both the groups favoring Lasmiditan 200 mg [OR: 0.88; 95% CI: 0.81-0.95]. CONCLUSION: An oral dosing of Lasmiditan 200 mg is ideal for the treatment of acute migraine in adult patients with CV risk factors for attaining headache pain freedom at 2 h and sustained pain freedom at 24 compared to Lasmiditan 100 mg.

Current concepts and clinical importance of glycemic variability.

BACKGROUND AND AIMS: Evolving evidence indicate that variations in blood glucose levels are likely to be an important factor in developing diabetic complications. Monitoring glucose fluctuations in patients remains as a therapeutic challenge and more evidence needs to be created in order to bring GV into limelight. This review encapsulates the most important findings conducted and discusses on them to provide readers a better understanding on this emerging subject. METHODS: Keyword-based comprehensive desktop search was conducted to gather the relevant literature. Triple-stage cascade type content analysis of the literature was conducted to draw relevant themes of discussions. RESULTS: High glycemic variability is associated with an increased risk of development of diabetic complications especially in cardiac conditions. The widely used and accepted metrics to determine the variations in blood glucose are Standard deviation (SD), MAGE (Mean amplitude of glycemic excursions) and MODD (Mean of daily differences). Occurrence of blood glucose variations affects at a molecular level thereby causing more harm than the occurrence of hyperglycemia alone. CONCLUSION: Available data suggest that Glycemic Variability should be used as an additional marker of glycemia. Additional research globally, and in India are required.

Pharmacogenomic phase transition from personalized medicine to patient-centric customized delivery.

Personalized medicine has been a booming area in clinical research for the past decade, in which the detailed information about the patient genotype and clinical conditions were collected and considered to optimize the therapy to prevent adverse reactions. However, the utility of commercially available personalized medicine has not yet been maximized due to the lack of a structured protocol for implementation. In this narrative review, we explain the role of pharmacogenetics in personalized medicine, next-generation personalized medicine, i.e., patient-centric personalized medicine, in which the patient's comfort is considered along with pharmacogenomics to be a primary factor. We extensively discuss the classifications, strategies, tools, and drug delivery systems that can support the implementation of patient-centric personalized medicine from an industrial perspective.

Assessment of Pharmacodynamic and Pharmacokinetic Interaction of Aqueous Extract of Cassia auriculata L. and Metformin in Rats.

BACKGROUND: Cassia auriculata L. (CA) leaf extract might increase the body's production of insulin thereby suppressing the elevated blood glucose and lipid levels in diabetic rats. CA has been used as dietary supplement in India from ancient times. OBJECTIVE: The present study was to elucidate the synergistic pharmacodynamic (PD) and pharmacokinetic (PK) interaction of metformin (MT) with CA. MATERIALS AND METHODS: A simple, precise reverse phase high performance liquid chromatography - UV detection mode method was developed to quantify MT in rat plasma. In PD interaction, streptozotocin (45mg/kg, intraperitoneally) induced diabetic Wistar rats weighing 180-250 g of either sex were randomized to receive MT (90 mg/kg, MT-HD), CA (500 mg/kg) separately and in combination of MT (90 mg/kg, MT-HD) + CA (500 mg/kg), and MT (45 mg/kg, MT-LD) + CA (500 mg/kg) (all oral) along with normal and diabetic control groups for 21 days. PK of MT was carried out in normal rats with preadministration of CA (500 mg/kg) for 14 days. RESULTS: PD data showed reasonable blood glucose lowering effect of CA. The reduction of MT dose with combination of CA achieved a similar blood glucose lowering effect of MT alone. PK data showed enhanced time taken to achieve maximum plasma concentration (Cmax), area under the curve (AUC0-t), and Cmax in combination group of MT (90mg/kg) and CA (500mg/kg), and reduction of MT dose in Group III had a reduced Cmax and AUC0-t compared to MT alone treated groups. CONCLUSION: Co-administration of CA with MT at varying dose showed a synergistic herb-drug interaction. Thus using the synergistic herb-drug interaction, the dose level of MT may be reduced to produce the same therapeutic effect as when taken alone. SUMMARY: Elucidating the synergistic pharmacodynamic (PD) and pharmacokinetic (PK) interaction of metformin (MT) with Cassia auriculata L. (CA)PD data showed reasonable blood glucose lowering effect of CA. The reduction of MT dose with combination of CA achieved a similar blood glucose lowering effect of MT alonePK data showed enhanced time taken to achieve maximum plasma concentration (Cmax), area under the curve (AUC0-t), and Cmax in combination group of MT and CA, and reduction of MT dose had a reduced Cmax and AUC0-t compared to MT alone treated groupsCo-administration of CA with MT at varying dose showed a synergistic herb-drug interaction. Thus using the synergistic herb-drug interaction, the dose level of MT may be reduced to produce the same therapeutic effect as when taken alone. Abbreviations used: CA: Cassia auriculata L., PD: Pharmacodynamic, PK: Pharmacokinetic, MT: Metformin, RP-HPLC-UV: Reverse phase High Performance Liquid Chromatography-UV detection mode, Tmax: Time taken to achieve maximum plasma concentration, AUC0-t: Area under the curve, Cmax: Maximum plasma concentration.

Screening of siddha medicinal plants for its in-vitro acetylcholinesterase and butyrylcholinesterase inhibitory activity.

BACKGROUND: The plants selected for the study were traditionally used in siddha system of medicine in neurological disorders. AIM: The aim of the following study isto screen the plant species for both acetylcholinesterase (AchE) and butyrylcholinesterase (BuchE) inhibition by in-vitro Ellman's method and a thin layer chromatography bioautographic assay for newer drug candidates for the treatment of Alzheimer's disease. MATERIALS AND METHODS: Ellman's colorimetric method was performed in a 96 well micro plate for cholinesterases inhibition using galantamine as standard drug. RESULTS: Present studies confirmed that out of all the tested extracts Hemidesmus indicus R.Br (HI) showed considerable IC50 values for AchE (28.40 ± 0.92 µg/mL) and BuchE (43.47 ± 0.64 µg/mL) inhibition which indicates that HI extract has considerable specificity toward AchE and BuchE compared with all the tested extracts and the activity was followed by Vernonia anthelmintica (VA) Willd and Saussurea lappa Clarke (SL). The bioautograms also confirmed the activity potent extracts. CONCLUSION: Besides various bioactivities HI, VA and SL exhibited considerable cholinesterases inhibition making it to consider these species for further investigation of new compounds.

Exploring the possible metabolism mediated interaction of Glycyrrhiza glabra extract with CYP3A4 and CYP2D6.

The rhizome of Glycyrrhiza glabra L. (licorice) is used very widely in Indian and Chinese traditional medicine, and it is a popular flavor ingredient of drinks, sweets and candies. Its medicinal uses include treating bronchitis, dry cough, respiratory infections, liver disorders and diabetes. Glycyrrhizin is normally considered to be its biologically active marker, so a rapid RP-HPLC method was developed for the quantitative estimation of glycyrrhizin in the extract. The effect of the standardized extract and its marker on drug metabolizing enzymes was evaluated through CYP3A4 and CYP2D6 inhibition assays to evaluate the safety through its drug interaction potential. The inhibition of CYP3A4 and CYP2D6 isozymes was analysed by the fluorescent product formation method. In the CYP450-CO assay, the interaction potential of the standardized extract and pooled microsomes (percentage inhibition 23.23 ± 1.84%), was found to be less than the standard inhibitor. In the fluorimetric assay, G. glabra extracts showed higher IC(50) values than their positive inhibitors, ketoconazole and quinidine for CYP3A4 and CYP2D6, respectively. Furthermore, the interaction potential of the plant extract was greater than the pure compound. The results demonstrate that G. glabra and its principle bioactive compound, glycyrrhizin, when co-administered with conventional medicines showed only a weak interaction potential with drug metabolizing enzymes.

Metabolism mediated interaction of α-asarone and Acorus calamus with CYP3A4 and CYP2D6.

The present study was aimed to investigate the possible interaction of the standardized extract of Acorus calamus (AC) with Cytochrome P450 enzyme, quantitative determination of the α-asarone in the AC rhizome was performed by RP-HPLC method. In vitro interaction of the plant extract was evaluated by CYP450-carbon monoxide complex (CYP450-CO) assay. Effect on individual isoforms such as CYP3A4 and CYP2D6 isozymes were analyzed through fluorescence product formation and respective IC(50) values were determined. CYP450-CO assay showed moderate interaction potential. Extract showed higher IC(50) values (46.84±1.83-32.99±2.21 µg/ml) comparing to the standard inhibitors and lower IC(50) value than α-asarone (65.16±2.37-42.15±2.45 µg/ml).

Assessment of impact of medication counseling on patients' medication knowledge and compliance in an outpatient clinic in South India.

The primary aim of this study was to assess the impact of patient medication counseling by comparing the levels of patient's medication knowledge and adherence achieved by medication counseling in an outpatient clinic. Ninety patients were randomized in the ratio of 1:2 into either counseled or usual care group. Their medication knowledge was assessed by a questionnaire and adherence was assessed by pill count method and self-assessment by the patients. Their medication knowledge was assessed at baseline and during their subsequent appointments. The average medication knowledge score of the counseled group versus usual care group was 13.82+/-1.8064 and 11.78+/-3.5037. Compliance score of the patients during their follow-up period was 92.29+/-4.5 and 84.71+/-11.80 for the counseled and control group, respectively. Statistical analysis of medication knowledge was carried out and all the demographic characters and number of medication were individually correlated with medication knowledge score and the difference observed was statistically significant. Compliance score of the patients was 92.29+/-4.5 and 84.71+/-11.8 % for the counseled and usual care group, respectively.