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Background: The effectiveness of intra-articular platelet-rich plasma (IA-PRP) injections for managing pain in knee osteoarthritis (KOA) remains inconsistent. Therefore, this study aimed to systematically review randomized controlled trials (RCTs) assessing the efficacy of IA-PRP., Methods: A total of 21 studies meeting the inclusion criteria were selected from various scientific databases, all of which compared PRP to either a placebo or an active comparator, such as corticosteroids (CS), in the treatment of KOA. Weighted mean differences (WMDs) for the Visual Analogue Scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Knee Injury and Osteoarthritis Outcome Score (KOOS), along with their 95 % confidence intervals (CIs), were calculated for each study. A subgroup analysis was conducted for the pain scores, comparing leukocyte-poor and leukocyte-rich PRP with either a placebo or CS. The evidence was synthesized using a random-effects meta-analysis., Results: There were 2406 participants in all included studies; 1223 were in the PRP versus placebo group and 1183 were in the PRP versus corticosteroid group. The IA-PRP showed significant improvement of VAS, and WOMAC scores compared to placebo (P < 0.00.05), except KOOS score (P > 0.05). All pain scores were highly sinficant improved with IA-PRP, compared to IA-CS (P < 0.05). Additionally, the leukocyte rich PRP was efficasious than leukocyte poor PRP (P < 0.05) improving the all pain scores at the 6-month follow-up., Conclusions: PRP treatment showed better results than placebo and corticosteroids in terms of reducing pain and improving function in KOA patients. Furthermore, lecocyte rich PRP is more effective than lecocyte poor PRP [PROSPERO, CRD42024540507]., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Ranakishor Pelluri reports statistical analysis was provided by Koneru Lakshmaiah Education Foundation. Ranakishor Pelluri reports was provided by Koneru Lakshmaiah Education Foundation. Ranakishor Pelluri reports a relationship with Koneru Lakshmaiah Education Foundation that includes: non-financial support. Koneru Lakshmaiah Education Foundation has patent pending to na. na If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Delhi Orthopedic Association. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

There is a molecular coupling between neurodegenerative diseases, including glaucomatous neurodegeneration (GN), Alzheimer's disease (AD), and Parkinson's disease (PD). Many cells in the eye and the brain have the right amount of 14-3-3 proteins (14-3-3 s) and their isoforms, such as β, ε, γ, η, θ, π, and γ. These cells include keratocytes, endothelial cells, corneal epithelial cells, and primary conjunctival epithelial cells. 14-3-3 s regulate autophagy and mitophagy, help break down built-up proteins, and connect to other proteins to safeguard against neurodegeneration in AD, PD, GN, and glioblastoma. By interacting with these proteins, 14-3-3 s stop Bad and Bax proteins from entering mitochondria and make them less effective. These interactions inhibit neuronal apoptosis. They play many important roles in managing the breakdown of lysosomal proteins, tau, and Aβ, which is why the 14-3-3 s could be used as therapeutic targets in AD. Furthermore, researchers have discovered 14-3-3 s in Lewy bodies, which are associated with various proteins like LRRK2, ASN, and Parkin, all of which play a role in developing Parkinson's disease (PD). The 14-3-3 s influence the premature aging and natural wrinkles of human skin. Studies have shown that lowering 14-3-3 s in the brain can lead to an increase in cell-death proteins like BAX and ERK, which in turn causes excitotoxicity-induced neurodegeneration. This review aimed to clarify the role of 14-3-3 s in the neuropathology of AD, PD, and GN, as well as potential diagnostic markers for improving neuronal survival and repair., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 Elsevier B.V. All rights reserved.)

To overcome the limits of traditional antibiotic medications, novel approaches are needed to combat the growing global epidemic of Multidrug-resistant (MDR) infections. As drug-resistant bacteria develop, the importance of innovative antimicrobial methods is underscored by antibiotic abuse and misuse. The global threat of MDR microorganisms is increasing, which calls for a coordinated global response. Lipid Nanoparticles (LNPs) possess several characteristics that make them attractive choices for managing multidrug resistant (MDR) infections, as well as potential delivery systems for antimicrobial agents. Thus, LNPs improve drug solubility, stability, and targeted delivery, thereby mitigating the drawbacks of conventional antibiotic therapy. Several characteristics of LNPs, which stop MDR bacteria from developing resistance mechanisms, serve as guidelines for precision medicine. It presents a powerful approach for combating the growing concern of MDR bacteria by increasing Anti-Microbial Peptides (AMPs) bioavailability and targeting distribution to bacterial cells. LNPs have the potential to redefine antibacterial treatments for MDR illnesses in the context of this study. Further, it discusses LNP use in larger applications, such as fighting Anti-Microbial Resistance (AMR) and MDR. A complete understanding of the unique features, many uses, and importance of collaborative efforts to overcome the global challenge of antibiotic resistance are also conveyed in the study., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The discovery of antivascular endothelial growth factor medications has resulted in a substantial change in diabetic retinopathy treatment. The most common cause of diabetic retinopathy blindness is Diabetic Macular Edema. The pathophysiology of Diabetic Macular Edema is thought to include the well-known pro-angiogenic and pro-permeability factor vascular endothelial growth factor. Over the past decade, drugs that impede the functions of vascular endothelial growth factors have established themselves as a standard-of-care treatment for a range of ocular ailments and improved patients' clinical results with diabetic retinopathy and Diabetic Macular Edema, and their frequency has grown exponentially with the introduction of these agents Pegaptanib, Ranibizumab, and Aflibercept which are approved for ophthalmic indications, while Bevacizumab is used off-label. These medications delivered intravitreally have halted the vascular development of diabetic retinopathy. Various randomized trials have proven that antivascular endothelial growth factor medication is safe and effective in preserving vision. Following an extensive period of preclinical development aimed at enhancing and defining its biological impacts, these drugs were shown in clinical trials to be effective in treating diabetic retinopathy and other ophthalmic conditions. Data from various sources suggest that Pegaptanib, Ranibizumab, and Aflibercept are costly, while Bevacizumab is cost-effective, and in low and middle-income nations, it is thus a desirable therapy choice. However, issues with compounding, counterfeiting, and off-label usage restrict its availability in many nations. The pharmacology, pharmacokinetics, pharmacodynamics, adverse effects, and contraindications of antivascular endothelial growth factor agents are discussed, and the results of clinical trials evaluating their efficacy are summarized., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., (© 2023. Fondazione Società Italiana di Neurologia.)

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.

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-1β, 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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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-β (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-β (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-β (1-42) peptides induced disrupted cognitive functions. Further, biochemical analysis showed that diosgenin successfully attenuated Amyloid-β (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 Aβ (1-42) induced neuronal damage and thereby can serve as a potential therapeutic candidate for AD., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Education plays a vital role not only in the management of diabetes but also for the effective prevention of diabetes and its complications. Prediabetes awareness and knowledge is grossly inadequate in India and massive prediabetic screening and management programs are urgently needed. This study was an initiative to conduct education program among the prediabetic subjects after assessment of their knowledge attitude and practice using a newly developed and validated prediabetes questionnaire. A total of 308 prediabetic participants were recruited through prediabetes screening camps conducted in the selected districts of Kerala and Tamilnadu. A newly developed and validated KAP-PAQ Questionnaire was used to analyze the Knowledge Attitude and Practice among the prediabetic population. The impact of Prediabetes Education Program was assessed by administration of questionnaire before and after PEP with an interval period of 30 days. Baseline assessment of knowledge among prediabetics shown that 90% had poor knowledge but after PEP program 43% had average knowledge and 44% could score good knowledge. Baseline assessment of attitude exhibited 30% with negative attitude but after counseling 68% shown positive attitude. Regarding practice assessment 35% had very poor and 52% shown poor practice but after PEP 71% shown good practice and 15% shown very good practice. Baseline KAP survey shows the need for health literacy among the newly diagnosed prediabetics. Prediabetes education program could bring significant improvement in knowledge attitude and practice and KAP-PAQ was found to be an efficient tool to conduct survey among the newly diagnosed prediabetics of south India., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier Inc.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Background: The current target of migraine treatment is focused on Triptans. Lasmiditan, a non-vasoconstrictive and highly selective 5HT 1F 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., Competing Interests: There are no conflicts of interest., (Copyright: © 2006 - 2021 Annals of Indian Academy of Neurology.)

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.

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.

Adverse drug reactions are considered to be among the leading causes of morbidity and mortality. Approximately 5-25% of hospital admissions are due to adverse drug reactions and 6-15% of hospitalized patients experience serious adverse drug reactions, causing significant prolongation of hospital stay. Thus this study was aimed at determining adverse drug reactions by conducting spontaneous reporting in secondary care Govt. District Head Quarters Hospital at Ooty. A prospective Spontaneous Adverse Drug Reaction reporting study was conducted over a period of 12 months from July 2012 to June 2013. The assessment, categorization, causality, severity and preventability were assessed using standard criteria. A total of 47 suspected adverse drug reactions were reported during the study period. Over all incidences was 1.29% among the study population. Antibiotics (31.91%) were the class of drug most commonly involved, while ciprofloxacin (14.89%) was the most frequently reported. Type H (Hypersensitivity) reactions (51.06%) accounted for majority of the reports and a greater share of the adverse drug reactions are probable (89.36%) based on causality assessment. Mild reactions accounted 82.97% based on modified Hartwig and Siegel severity scale. In 76.59% of the reports, the reaction was considered to be preventable based on Schumock and Thornton preventability scale. The implementation of monitoring based on spontaneous reporting will be useful for the detection and evaluation is associated with increase in morbidity and duration of hospitalization. This study also has established the vital role of clinical pharmacist in the adverse drug reaction monitoring program.

Objective: To ascertain the trend of poisoning cases admitted to the Government District Headquarters Hospital, a secondary care center in Udhagamandalam, Nilgiris District, Tamil Nadu, India, over a five-year period., Materials and Methods: The number of cases that presented to the hospital annually (incidence, mortality, and case fatality rates), socio-demographic pattern, and the nature of the poison were noted., Results: A total of 1860 poisoning cases (80 deaths) were reported during the period from October 2008 to September 2013. The incidence of poisoning was found to increase every year. The average incidence was 1.60 per 1000 population, while the average case fatality rate and mortality rates were 40.51 and 0.07, respectively. A total of 1148 (62%) were males. The majority of cases were seen in the 21-30 age group (41.24%). The poisonings were largely deliberate self-harm (n = 1,755; 94.35%), followed by accidental (n = 85; 4.57%). Agrochemicals were the main choice of poisoning agents and among these, organophosphates were the major cause., Conclusion: The data generated can help policy makers take decisions on the sale and availability of pesticides in this region.

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.

Ethnopharmacological Relevance: Calotropis gigantiea (L.) R. Br (Apocynaceae) commonly called as "crown flower" or "giant milk weed" is a well-known weed to many cultures for treating various disorders related to central nervous system, skin diseases, digestive system, respiratory system, reproductive system etc. Indigenous groups made the plant as a part of their lives since they use the fruit fibre to make ropes, household items, for weaving clothes and flowers for garlands apart from usage for various indications. The study aims at far-reaching review on phytochemistry, pharmacological activities, ethnopharmacology, intellectual property transfer on pharmacological therapies, toxicity which aids to provide scientific evidence for the ethnobotanical claims and to identify gaps required to be conducted as a future research prerequisite., Materials and Methods: A systematic literature search was performed using different databases such as Scopus, Science direct, PubMed and Sciverse with no timeline limit set during the search. All the available abstracts and full text articles were included in the systematic review., Results: Most of the folkloric uses were validated by the scientific studies such as analgesic, anti-arthritic, anti-asthmatic, anti-bacterial, anti-convulsant, anti-pyretic, central nervous system disorders, contraceptive, anti-ulcer and wound healing. In addition other studies such as anti-diabetic, anti-diarrhoeal, anti-helminthic, anti-histamine, anti-inflammatory, anti-microbial, anti-oxidant, cardio-protective studies, cytotoxicity, hepatoprotectivity, fibrinolytic, mosquitocidal, nerve muscle activity, vasodilation and skeletal muscle activities were also reported for the plant. Isolated compounds such as calotropin, frugoside and 4'-O-β-D-glucopyranosyl frugoside were tested for the cytotoxicity efficacy against both human and rat cell lines out of which calotropin showed potent activity (IC50-15 ng/ml). However there were no clinical trials reported on the plant which is one of the major lacunas., Conclusions: This review article explores the ethnopharmacological, pharmacological activities phytochemistry and intellectual rights of Cg which gives the evidence of a potent and commercial drug which up on further research leads to the most viable drug for variety of treatments. However there is further need for in-vivo studies and clinical trials on isolated phytoconstituents which will help to commercialise., (© 2013 Published by Elsevier Ireland Ltd.)

Breast cancer is the foremost common malignancy among the female population around the world. Female breast cancer incidence rates have increased since 1980, slowed in 1990, the rate of increase have leveled off since 2001. In spite of the advances in the early detection, treatment, surgery and radiation support, almost 70% of the patients develop metastasis and die of the disease. Around 10% of the patients when diagnosed with breast cancer have metastases. Survival among the breast cancer patients have increased due to the introduction of novel single agent, combination of chemotherapeutic agents and targeted biologic agents, which is breast cancer specific. The staging of tumor-node-metastasis is significant for the prognosis and treatment. Predominantly the combination of chemotherapeutic regimen is given to improve the rate of clinical benefit and the overall survival rate. Novel mono-therapeutic options are being used often in metastatic setting as they will not be able to endure the toxicity of the combination regimen. Usually, endocrine therapy is recommended for hormone-responsive breast cancer due to efficacy and favorable side effect profile but chemotherapy becomes an option when endocrine therapy fails. This review summarizes the newer therapeutic options for early breast cancer and advanced breast cancer that are pretreated heavily on other chemotherapeutic agents. Further it provides monotherapies and other emerging novel combination regime which can be opted for first line or second line setting.

Botanicals fall under different regulations in different countries and are mostly consumed without the consultation of the healthcare professional. Over the last decade, utilization of herbal therapies has been extensively documented. The findings indicate the possibility of potential herb-drug interactions due to the concomitant administration of herbal extracts and prescription/over-the-counter drugs. Simultaneously, with the increasing public awareness and search for safer herbal remedies, the study on herbal-drug interactions has gained momentum through the study of drug metabolizing enzymes. Cytochrome P450 (CYP) inhibition or induction is probably the most common mechanism for the pharmacokinetic interactions of herbs and drugs. Any inhibition of CYP enzymes by herbal extracts may result in enhanced plasma and tissue concentration of drugs, leading to toxicity, while induction results in reduced drug concentration leading to decreased drug efficacy and treatment failure. Considering the rapidly growing herbal markets, these types of clinical interactions remain under-reported and unclear. With the increasing consumption of herbal extracts along with prescription medicines, the safety of herbs has become a concern. This article reviews the potential for drug interactions by herbal extracts through drug metabolizing enzymes., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2011 John Wiley & Sons, Ltd.)

Murraya koenigii leaves (Rutaceae) are widely used as food condiments in various food preparations in India. They possess a wide range of biological activities including antioxidant, antibacterial, anticancer, hypoglycemic and hypolipidemic activity. A rapid reverse-phase high-performance liquid chromatography (RP-HPLC) method has been developed for quantitative estimation of mahanine and mahanimbine, two major bioactive alkaloids in this plant. The amounts of mahanine and mahanimbine were detected as 9.56 ± 1.04 and 4.32 ± 0.81% w/w in the extract, with the retention times of 6.26 ± 0.66 and 10.40 ± 0.95 minutes. The limits of detection and quantification were estimated to be 29.30 and 81.12 µg/mL and 1.67 and 6.31 µg/mL, respectively. This specific and precise validated method can be useful for the routine analysis and quantitative determination of mahanine and mahanimbine in this therapeutically potent medicinal plant., (Copyright © 2011 John Wiley & Sons, Ltd.)

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)., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: 'Triphala' is one of the age-old, most commonly used polyherbal preparation from Ayurveda as Rasayana drug., Aim of the Study: This study was aimed at evaluating the effect of 'Triphala' on drug modulating enzymes to assess its safety through its potential to interact with co-administered drugs., Materials and Methods: The cytochrome P450 inhibitory effect of 'triphala' formulation was investigated on rat liver microsomes using CYP450-CO complex assay and on individual isoform such as CYP3A4 and 2D6 using fluorescence screening. RP-HPLC method was developed to standardize 'triphala' and its individual components using gallic acid as analytical marker compound., Results: RP-HPLC analysis demonstrated the presence of gallic acid (4.30±2.09 mg/g) in the formulation. The formulation showed 23% inhibition of the rat liver microsomes through CYP450-CO complex assay which is comparatively less when compared with the individual components. Further, the effect of standardized formulation dissolved in ethanol showed CYP3A4 and CYP2D6 inhibitory activity at the IC(50) values of 119.65±1.91 μg/ml and 105.03±0.98 μg/ml respectively. Gallic acid was also found to inhibit both the isoforms at the IC(50) values of 87.24±1.11 μg/ml and 92.03±0.38 μg/ml respectively., Conclusions: Various concentrations of the formulation and its individual components showed significantly less inhibitory activity (p<0.001) on individual isoforms when compared with the positive control. Assessment on the in vitro effect of 'triphala' on drug modulating enzymes has important implications for predicting the likelihood of herb-drug interactions if these are administered concomitantly., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

The hydroalcoholic extract of fruit pulp of Terminalia chebula Retz. was standardized and evaluated for its safety through cytochrome P450 (CYP 450) inhibition assay. Standardization was performed through high performance thin layer chromatography (HPTLC) using gallic acid (GA) standard. Cytochrome P450-CO complex microplate assay was performed using rat liver microsomes. The effect of standardized extract, its fraction and bioactive marker compound were comparatively evaluated for its effect on CYP P450 enzymes. The extract of fruit pulp was used for HPTLC, where the R(f) value of the marker was found to be 0.43. The calibration plot was linear in the range of 2-14 µg of GA and correlation co-efficient of 0.99965. The mean quantity of GA was found to be 2.5% w/w. The CYP P450 concentration of the rat liver microsome sample used in the study was found to be 0.417 nmol/mg protein. The in vitro effect of various concentrations of extracts and fractions showed a linear concentration-dependent inhibition of cytochrome P450 up to 60 µL. The study showed more inhibition of fraction when compared to the extract and GA. Still, the inhibition showed by fraction is less when compared with standard Ketoconazole. Thus, this study indicated the in vitro cytochrome P450 inhibition potential of T. Chebula., (Copyright © 2010 John Wiley & Sons, Ltd.)

Traditional systems of medicines need more evidence-based studies on both crude drugs and purified phytomolecules. Utilization of natural products as pharmacological tools could lead to a number of new major therapeutically active metabolites. Lead molecules are further screened for their potential in terms of quality control, safety assessments, and studies about molecular pharmacology and their related properties. Identification, and quality and safety evaluation of natural products, is a fundamental requirement of industry and other organizations dealing with natural health products (NHPs). Marker analysis, based on chemo-profiling and development of characteristic fingerprints for individual plants, could help to develop uniform standardization tools. Beside such evaluations of clinical parameters, safety profiles as well as drug-herb and herb-herb interactions are the most important parameters for assessment and promotion. With the steady growth of the NHPs, advanced analytical- and mechanism-based screening should be considered for their promotion and value addition in every way for the betterment of healthcare. Thus, there is an urgent need for the development of international co-ordination to promote and develop NHPs, including their assessment, perspectives, pharmacovigilance, and potential harmonization of regulation, quality control and clinical uses.

Background: Several lead compounds have been developed from natural resources as hepatoprotective. The hepatotoxic nature of the drugs, industrial toxins and drug-induced hepatotoxicity has been recognized as the major problem associated with liver diseases. Natural products including herbs have great potential in treating liver disorders., Objective: Botanicals have been used traditionally by herbalists and indigenous healers worldwide for several years for the prevention and treatment of liver disease and clinical research in this century has confirmed the efficacy of several plants in the treatment of liver disease. Many herbs used in several systems of alternative medicines have a long history of traditional use in revitalizing the liver and treating liver dysfunction and disease. Many of these herbs have been evaluated in clinical studies and are now being investigated phytochemically to understand their actions in a better way., Conclusion: An attempt has been made through this article to review the most potential medicinal plants with pharmacologically established hepatoprotective activity. Further, this article highlights their phytochemical profile and finds the effective leads from natural resources for the desired therapeutic benefit.

Methanolic extracts of leaf, root, flower and aerial parts of Hypericum hookerianum were assessed for in vitro antioxidant activity using eight different models. Total antioxidant capacity, phenol and flavanol content of the extracts were determined to correlate between their antioxidant activity and constituents present therein. Results of in vitro antioxidant study suggest that extracts from leaf and flower have strong antioxidant potential. Leaf extract (100 & 200 mg kg(-1) b.w. p.o.) that showed maximum activity was selected for in vivo antioxidant studies using a CCl(4)-intoxicated rat model. The effects of extracts on lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) in serum and liver homogenate were analysed. CCl(4) treatment caused a significant increase in the level of CAT and SOD and a significant decrease in the level of LPO in a dose-dependent manner when compared to CCl(4) treated control. The results indicate the strong antioxidant nature of H. hookerianum leaf extract.

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.

The therapeutic profile of many anti-cancer drugs has been improved by their modified distribution through a colloidal carrier system. Hence, bovine serum albumin nanospheres containing 5-fluorouracil were prepared by pH-coacervation methods. To select the most suitable cryoprotector for the formulated nanosphere system, a study on the effect of cryoprotectors in the prevention of particle agglomeration was done. Using glucose and mannitol at various concentrations during freeze drying, glucose at a concentration of 5% was observed to be relatively more effective in the prevention of particle agglomeration than the other cryoprotectors. The carrier capacity was determined through the drug-to-albumin ratio. The particle size of all the drug-loaded batches was analyzed before and after freeze drying. The batch of nanospheres with uniform size distribution, and highest drug loading, was used for other subsequent studies. The effect of surfactant in drug loading was estimated through various concentrations of sodium lauryl sulfate, and it was observed that the surfactant has no influence on drug loading at the selected concentrations. The batch of nanospheres with highest drug loading was evaluated for its in-vitro release, and the drug release was found to be in a bi-phasic pattern. To evaluate the efficacy of 5-fluorouracil-loaded nanospheres against cancer cells, an in vitro cytotoxicity study was carried out using HEp-2 cell lines. The nanosphere-bound drug was observed to produce a better cytotoxic effect than the free drug. The anti-tumor efficacy of drug-loaded nanosphere was investigated in DLA tumor-induced mice models, and the percentage tumor inhibition was relatively higher in animals treated with nanosphere-bound drug than with free drug.

Nanospheres made from natural hydrophilic polymers have been proved efficient in terms of better drug-loading capacity, biocompatibility, and possibility less opsonization by reticuloendothelial system (RES) through an aqueous stearic barrier. Hence, nanospheres containing methotrexate were prepared from bovine serum albumin (BSA) by a novel pH coacervation method. A drug-to-polymer ratio study was carried out to determine the carrier capacity. The batch with the highest drug loading was subjected to in vitro analysis. It was found to provide a slow release after an initial burst release. Biodistribution of nanosphere-bound drug was compared with that of free drug in mice. It was observed that the percentage increase in drug distribution to the lungs, liver, and spleen was markedly high from the nanosphere when compared to free drug.

The stability of liposomes after introduction into the body is presently being discussed and needs thorough understanding. Hence, as a nonliposomal approach, egg albumin nanospheres were prepared by the pH-coacervation method, and a preliminary study was carried out of the influence of process variables on the size and shape of nanospheres by changing the pH of the albumin solution, concentration of albumin solution, and volume of cross-linking agent. The batch prepared with an albumin medium of pH 9, 2% concentration, and 100 microliters of 4% glutaraldehyde-ethanol solution was found to have a spherical uniform shape with an average size of 497.6 nm. The ideal batch was loaded with the systemic antifungal drug amphotericin-B. Drug-loaded nanospheres were evaluated to study their in vitro release. They were found to exhibit a biphasic pattern with a cumulative percentage release of 97.7%.