Plumbagin Alleviates Intracerebroventricular-Quinolinic Acid Induced Depression-like Behavior and Memory Deficits in Wistar Rats.

Plumbagin, a hydroxy-1,4-naphthoquinone, confers neuroprotection via antioxidant and anti-inflammatory properties. The present study aimed to assess the effect of plumbagin on behavioral and memory deficits induced by intrahippocampal administration of Quinolinic acid (QA) in male Wistar rats and reveal the associated mechanisms. QA (300 nM/4 µL in Normal saline) was administered i.c.v. in the hippocampus. QA administration caused depression-like behavior (forced swim test and tail suspension tests), anxiety-like behavior (open field test and elevated plus maze), and elevated anhedonia behavior (sucrose preference test). Furthermore, oxidative-nitrosative stress (increased nitrite content and lipid peroxidation with reduction of GSH), inflammation (increased IL-1ß), cholinergic dysfunction, and mitochondrial complex (I, II, and IV) dysfunction were observed in the hippocampus region of QA-treated rats as compared to normal controls. Plumbagin (10 and 20 mg/kg; p.o.) treatment for 21 days significantly ameliorated behavioral and memory deficits in QA-administered rats. Moreover, plumbagin treatment restored the GSH level and reduced the MDA and nitrite level in the hippocampus. Furthermore, QA-induced cholinergic dysfunction and mitochondrial impairment were found to be ameliorated by plumbagin treatment. In conclusion, our results suggested that plumbagin offers a neuroprotective potential that could serve as a promising pharmacological approach to mitigate neurobehavioral changes associated with neurodegeneration.

Isolation, chemical characterization, antimicrobial activity, and molecular docking studies of 2,6-dimethoxy benzoquinone isolated from medicinal plant Flacourtia jangomas.

In the present investigation one compound, 2,6-dimethoxy benzoquinone (FJL-1), was isolated from the dichloromethane (DCM) fraction of the organic leaf extract of Flacourtia Jangomas for the first time. The compound structure was elucidated using extensive spectral analysis, including 1H, and 13C NMR. Furthermore, the DPPH and ABTS methods were used to evaluate the antioxidant activity of the organic extract, its fractions, and the isolated compound FJL-1. Antioxidant activity of the petroleum, ether, DCM, and methanol fractions of the organic extract and the isolated compound of F. Jangomas revealed moderate to strong radical scavenging ability. Additionally, the antimicrobial activity of FJL-1 against Staphylococcus aureus (MTCC 737 and MTCC 96 strains) was observed in an inhibition zone size of 21.6 ± 0.6 to 21.7 ± 0.58 mm showing potential inhibitory activity. The isolated compound FJL-1 shows excellent binding with the 2W9S proteins in terms of docking score compared with the drug Trimethoprim, which also exhibited similar types of interaction and potency against S. aureus. The leaves of F. jangomas can be considered a great source for the identification of numerous important phytoconstituents with potential uses in nutrition, aromatherapy, and the pharmaceutical sector. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-04002-w.

Therapeutic Implications of Dietary Polyphenols-Loaded Nanoemulsions in Cancer Therapy.

Cancer is one of the major causes of death worldwide, even the second foremost cause related to non-communicable diseases. Cancer cells typically possess several cellular and biological processes including, persistence, propagation, differentiation, cellular death, and expression of cellular-type specific functions. The molecular picture of carcinogenesis and progression is unwinding, and it appears to be a tangled combination of processes occurring within and between cancer cells and their surrounding tissue matrix. Polyphenols are plant secondary metabolites abundant in fruits, vegetables, cereals, and other natural plant sources. Natural polyphenols have implicated potential anticancer activity by various mechanisms involved in their antitumor action, including modulation of signaling pathways majorly related to cellular proliferation, differentiation, relocation, angiogenesis, metastatic processes, and cell death. The applications of polyphenols have been limited due to the hydrophobic nature and lower oral bioavailability that could be possibly overcome through encapsulating them into nanocarrier-mediated delivery systems, leading to improved anticancer activity. Nanoemulsions (NEs) possess diverse feasible properties, including greater surface area, modifiable surficial charge, higher half-life, site-specific targeting, and formulation imaging capability necessary to create a practical therapeutic impact, and have drawn increased attention in cancer therapy research. This review has summarized and discussed the basic concepts, classification, delivery approaches, and anticancer mechanism of various polyphenols and polyphenols-encapsulated nanoemulsions with improved cancer therapy.

The Design, Development, and Implementation of a Web-Enabled Informatics Platform to Enhance the Well-being of Individuals Aged 18-24 Years: Protocol for an Experimental Study.

BACKGROUND: Well-being is multidimensional, complex, and dynamic in nature. It is an amalgam of physical and mental health, essential for disease prevention and the promotion of a healthy life. OBJECTIVE: This study aims to explore the features that impact the well-being of individuals between 18 and 24 years of age in an Indian setting. It further aims to design, develop, and evaluate the usefulness and effectiveness of a web-based informatics platform or stand-alone intervention to enhance the well-being of individuals aged 18-24 years in an Indian setting. METHODS: This study follows a mixed method approach to identify factors influencing the well-being of individuals in the age group of 18-24 years in an Indian setting. The college-going students in this age group from the states of Uttarakhand (urban settings of Dehradun) and Uttar Pradesh (urban settings of Meerut) will be enrolled. They will be randomly allocated to the control and intervention groups. The participants in the intervention group will have access to the web-based well-being platform. RESULTS: This study will examine the factors that influence the well-being of individuals aged 18-24 years. It will also facilitate the design and development of the web-based platform or stand-alone intervention, which will enhance the well-being of individuals in the age group of 18-24 years in an Indian setting. Furthermore, the results of this study will help generate a well-being index for individuals to plan tailored interventions. The 60 in-depth interviews have been conducted as of September 30, 2022. CONCLUSIONS: The study will help understand the factors that influence the well-being of individuals. The findings of this study will help in the design and development of the web-based platform or stand-alone intervention to enhance the well-being of individuals in the age group of 18-24 years in an Indian setting. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/38632.

Navigating the Solution to Drug Formulation Problems at Research and Development Stages by Amorphous Solid Dispersion Technology.

Amorphous Solid Dispersions (ASDs) have indeed revolutionized the pharmaceutical industry, particularly in drug solubility enhancement. The amorphous state of a drug, which is a highenergy metastable state, can lead to an increase in the apparent solubility of the drug. This is due to the absence of a long-range molecular order, which results in higher molecular mobility and free volume, and consequently, higher solubility. The success of ASD preparation depends on the selection of appropriate excipients, particularly polymers that play a crucial role in drug solubility and physical stability. However, ASDs face challenges due to their thermodynamic instability or tendency to recrystallize. Measuring the crystallinity of the active pharmaceutical ingredient (API) and drug solubility is a complex process that requires a thorough understanding of drug-polymer miscibility and molecular interactions. Therefore, it is important to monitor drug solids closely during preparation, storage, and application. Techniques such as solid-state nuclear magnetic resonance (ssNMR), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), Raman spectroscopy, and dielectric spectroscopy have been successful in understanding the mechanism of drug crystallization. In addition, the continuous downstream processing of drug-loaded ASDs has introduced new automated methods for consistent ASD production. Advanced techniques such as hot melt extrusion, KinetiSol, electro spraying, and electrospinning have gained popularity. This review provides a comprehensive overview of Amorphous Solid Dispersions (ASDs) for oral drug delivery. It highlights the critical challenges faced during formulation, the impact of manufacturing variables, theoretical aspects of drug-polymer interaction, and factors related to drug-polymer miscibility. ASDs have been recognized as a promising strategy to improve the oral bioavailability of poorly water-soluble drugs. However, the successful development of an ASD-based drug product is not straightforward due to the complexity of the ASD systems. The formulation and process parameters can significantly influence the performance of the final product. Understanding the interactions between the drug and polymer in ASDs is crucial for predicting their stability and performance.

A Promising Approach of Dermal Targeting of Antipsoriatic Drugs via Engineered Nanocarriers Drug Delivery Systems for Tackling Psoriasis.

Psoriasis is a complex autoimmune skin condition with a significant genetic component. It causes skin inflammation and is characterized by flaky, silvery reddish spots that can worsen with age. This condition results from an impaired immunological response of T-cells and affects 2-5% of the global population. The severity of the illness determines the choice of treatment. Topical treatments are commonly used to treat psoriasis, but they can have several adverse effects. Biological therapy is another option for treating specific types of psoriasis. Recently, new nanoformulations have revolutionized psoriasis treatment. Various nanocarriers, such as liposomes, nanostructured lipid nanoparticles, niosomes, and nanoemulsions, have been developed and improved for drug delivery. The use of nanocarriers enhances patient compliance, precise drug delivery, and drug safety. This review aims to suggest new nanocarrier-based drug delivery systems for treating psoriasis. It discusses the importance of nanocarriers and compares them to traditional treatments. Anti-psoriatic drugs have also been investigated for cutaneous delivery using nanocarriers. The review also covers various factors that influence dermal targeting. By highlighting several relevant aspects of psoriasis treatment, the review emphasizes the current potential of nanotechnology. Using nanocarriers as a drug delivery technique may be a promising alternative treatment for psoriasis.

Dihydroartemesinin and Curcumin Based Self-Microemulsifying Drug Delivery System for Antimalarial Activity.

Malaria is a significant global problem which still persists despite the development of various effective antimalarial drugs. It is challenging to treat this disease due to the parasite's complex life cycle and high recrudensce of antimalarial drugs. A new self-micro emulsifying drug delivery system has been developed to improve the solubility of dihydroartemisinin and curcumin. The prepared formulation contained Dihydroartemesinin, curcumin, Groundnut Oil, Cremephor RH, and Tween 80. Self-micro emulsification time, zeta potential, droplet size, polydispersity index, transmission electron microscopy, drug release, and in-vivo studies were performed for characterization. The globule size was found to be 25.59±0.40 nm and the zeta potential was-5.75±0.18 mV. The globules prepared were spherical in shape. The in-vitro dissolution performance of formulation of dihydroartemisinin and curcumin self emulsifying drug delivery system showed significantly (p<0.05, Origin Pro 8.5) higher release as compared to the pure drugs. The results of the study suggested that the prepared self emulsifying drug delivery system combination of Dihydroartemesinin and curcumin has a better potential to cure parasitemia as compared to the individual drug.

Traumatized periosteum: Its histology, viability, and clinical significance.

The periosteum covers the surface of long bone except at the joints. During fracture fixation, we found the periosteum is ragged and damaged. Our objective is to determine the microscopic picture of traumatized periosteum in terms of the degree of damage, cell type, stromal tissue, and vascularity. Periosteum of 1cm*1cm is harvested at 1cm, 3cm, and 5cm proximal and distal to fracture site following fracture of a long bone in 20 humans. Ragged and damaged periosteum mainly consists of an outer fibrous layer with many hemorrhagic tissue and neovascularization. Osteoprogenitor cells were seen only in 12 out of 97 samples, mostly harvested 5 cm from the fracture site. The innermost layer of the periosteum remains attached to the bone surface after separating the fibrous layer following a fracture. The use of a periosteal elevator on the bone surface further damages the inner layer of the periosteum. Using a scalpel to separate the periosteum or merely pulling it away from the bone surface will decrease damage to the inner cambium layer. Fracture reduction can be achieved by indirect means at least 5 cm away from the fracture site.

Current Updates in Transdermal Therapeutic Systems and Their Role in Neurological Disorders.

The transdermal therapeutic system plays an important role in the treatment of neuropathic pain. Transdermal drug delivery is considered an ideal therapeutic approach for the management of chronic neurological disorders in the elderly population. It is a simple to use, non-invasive and painless drug delivery system, which provides sustained therapeutic plasma levels of drug for an extended period. Moreover, it bypasses the first-pass metabolism of the active agent, improves bioavailability and reduces undesired adverse effects, which in turn improves patient compliance. Several transdermal delivery systems are currently under investigation for the treatment of Parkinson's syndrome, Alzheimer's disorders, and Neurological pain. Drug delivery via the transdermal route is proposed as an alternative remedy to overcome the drawbacks associated with the conventional dosage forms for chronic neurological disorders. The management of Alzheimer's disease via transdermal drug administration exhibits the greatest therapeutic improvements in the treatment of cognition and global functioning among neuropathic patients. Technological breakthroughs in transdermal drug administration such as the microreservior system, microneedles, metered-dose transdermal spray (MDTS), needle-free injections, and ultrasound-based transdermal therapeutic systems have been successfully used to treat neurological disorders. For example, microneedle (MN) is a highly efficient and versatile device due to its distinctive properties. Ultrasounds have been very popular for the delivery of bioactive agents across the skin barrier. This review focuses on the recent advances of various technologies employed in the transdermal therapeutic systems and their applications on neurological disorders for achieving therapeutic outcomes on patients.

Effect of selected group of asana when used as an adjunct in management of cervical spondylosis of mild to moderate severity: An observational study.

BACKGROUND: "Cervical spondylosis" (CS) is a collective term used for non-specific neck pain post 30 age group. Management of CS is mainly non-surgical, particularly in mild to moderate severity that includes the oral anti-inflammatory drugs, exercises, manipulation, mobilization, or combination of these. OBJECTIVE: The objective of the study is to assess the possible benefit of a selected group of asana in a group of patients over a short time frame and assess their functional outcome. MATERIALS AND METHODS: An observational study of cohort of patients having mild to moderate CS, who visited the AYUSH department between May 2016 and November 2016 were included. "Selected group of Asana (SGOA)" was practiced for 30 min supervised and then home-based for a period of 8 weeks with usual standard treatment. Patients followed up fortnightly, and their degree of severity & disability assessed. RESULTS: Thirty patients with 19 males and 11 females having ages mean ± SD 45.61 ± 8.3 and 44.18 ± 9.78 having NDI score of mean ± SD 17.83 ± 4.749 at baseline (0 weeks) were included. Patients showed an improvement in NDI score to finally 7.40 ± 3.180, p-value = 0.0001. This improvement was also noted at various time intervals (p-value = 0.0001 each time), as seen in the post hoc analysis. CONCLUSION: Yogic practices "Specific Group of Asana" done for eight weeks on a home-based program could be useful in reducing pain and disability in people suffering from CS of mild to a moderate degree. However, more extensive, comparative, and multi-centric trials are required for establishing this as a treatment modality.

Potential role of nicotinamide analogues against SARS-COV-2 target proteins.

BACKGROUND AND OBJECTIVE: Coronavirus 2019 (COVID-19) is caused by 'severe acute respiratory syndrome coronavirus 2' (SARS-CoV-2), first reported in Wuhan, China in December 2019, which eventually became a global disaster. Various key mediators have been reported in the pathogenesis of COVID-19. However, no effective pharmacological intervention has been available to combat COVID-19 complications. The present study screens nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) as potential inhibitors of this present generation coronavirus infection using an in-silico approach. MATERIALS AND METHODS: The SARS-CoV-2 proteins (nucleocapsid, proteases, post-fusion core, phosphatase, endoriboruclease) and ACE-2 protein were selected. The 2D structure of nicotinamide ribonucleoside and nicotinamide ribonucleotide was drawn using ChemDraw 14.0 and saved in .cdx format. The results were analyzed using two parameters: full fitness energy and binding free energy (ΔG). RESULTS: The full fitness energy and estimated ΔG values from docking of NM, and NMN with selected SARS-CoV-2 target proteins, ADMET prediction and Target prediction indicate the interaction of NR and NMN in the treatment of COVID-19. CONCLUSIONS: Based on full fitness energy and estimated ΔG values from docking studies of NM and NAM with selected SARS-CoV-2 target proteins, ADME prediction, target prediction and toxicity prediction, we expect a possible therapeutic efficacy of NR in the treatment of COVID-19.

Production variables affecting characteristics of pellets in melt pelletization with wax combination in a laboratory scale spheronizer.

The purpose of the study was to evaluate the suitability of laboratory scale spheronizer for the production of spherical pellets loaded with diltiazem hydrochloride by wax combination. The 1:1 combination of cetyl alcohol and hydrogenated castor oil, as low and high melting point waxes, were used. The various production variables affecting the different characteristics of pellets and the process efficiency were evaluated. Drug loaded pellets were evaluated for drug release in distilled water. Bowl temperature primarily affects the sphericity and adhesion of pellets to the bowl. Mass temperature has a pronounced effect on size, size distribution and sphericity of pellets. Wax concentration affects all characteristics of pellets but adhesion was least affected. The effect of these three variables can be compensated by optimizing the friction plate speed. It has been found that the highest yield of pellets (850--1400 microm) with maximum sphericity can be produced by using 45 degrees C bowl temperature, 52 degrees C mass temperature and 1400 rpm friction plate speed.

Enhanced bioavailability of cinnarizine nanosuspensions by particle size engineering: Optimization and physicochemical investigations.

Cinnarizine (CIN), a poorly soluble drug with erratic bioavailability due to pH dependent solubility has limited advantage to formulate oral solid dosage forms in subject having low gastric acidity. In present study precipitation-ultrasonication was used to fabricate nanosuspensions of cinnarizine stabilized by Poly vinyl alcohol (PVA) to enhance the bioavailability. We investigated the effects of PVA concentration (X1) and solvent to antisolvent ratio (X2) on the quality attributes like mean particle size (Y1); % drug content (Y2); and time required to 90% drug release (Y3) via 3(2) factorial design. The morphology of nanosuspensions was found almost spherical by SEM observation. DSC and FT-IR studies revealed lack of significant interactions between CIN and PVA. Nanosuspensions of mean particle size 621.08 nm was achieved. The dissolution rate obtained from all formulations were markedly higher than pure CIN. Response surface methodology and optimized polynomial equations were used to select the optimal formulation i.e. 0.2% W/V of X1 and 1:42 of X2 to get the desired response Y1; 636.78 nm, Y2; 95.24% and Y3; 7.09 min that were in reasonable agreement with the observed value. The in-vivo study in rat demonstrated that Cmax and AUC0→12 values of nanosuspension were approximately 2.8-fold and 2.7-fold greater than that of reference preparation respectively.

Formulation and process optimization of naproxen nanosuspensions stabilized by hydroxy propyl methyl cellulose.

In present study precipitation-ultrasonication was used to obtain nanosuspensions of poorly water-soluble drug, naproxen (NPX). We investigated the effects of HPMC concentration (X1) and time of ultrasonication (X2) on imperative attributes like mean particle size (Y1), % drug content (Y2), and time required to 90% drug release (Y3) via 3(2) factorial design. The morphology of nanosuspensions was found almost spherical by SEM observation. DSC and XRD studies suggested slight crystalline change in drug. FT-IR revealed lack of significant interactions between NPX and HPMC. Nanosuspensions of mean particle size 530.55 nm was achieved. Dissolution rate obtained from all nanosuspensions were markedly higher than pure NPX. Response surface methodology and optimized polynomial equations were used to select optimal formulation i.e. 1.36%W/V of X1 and 13.9 min of X2 to get desired response Y1; 727.97 nm, Y2; 95.59% and Y3; 8.67 min that were in reasonable agreement with observed value.

Therapeutic evaluation of "Ayush Tulsi Jiwan Plus" oil for chronic musculoskeletal pain relief.

BACKGROUND: Chronic pain of musculoskeletal origin is a very common symptom and has major effect on the physical, mental, and economic aspects of the patients. There is always a crave among physicians and patients for effective analgesic, curable preparation that can be locally applied. AIM: The aim of this study is to assess the efficacy and safety of "Ayush Tulsi Jiwan Plus" oil in chronic pain management of musculoskeletal origin. MATERIALS AND METHODS: Fifty patients of chronic musculoskeletal pain of unknown origin of mild to moderate condition were advised to apply "Ayush Tulsi Jiwan Plus" oil locally twice daily for 6 weeks and examined weekly. After completion of the treatment, the efficacy of the therapy was assessed on the basis of the subjective criteria such as perception of pain, tenderness, swelling, and joint mobility. RESULTS: In this study, mean baseline score versus last visit score of pain (2.84 ± 0.68 vs. 1.33 ± 0.76), tenderness (1.64 ± 0.74 vs. 0.36 ± 0.56), and swelling (0.64 ± 0.85 vs. 0.38 ± 0.66) was significantly decreased, and also clinical improvement was seen in the study participants along with no evidence of adverse drug reactions. CONCLUSION: The analysis of the overall effect of this "Ayush Tulsi Jiwan Plus" oil preparation was found efficacious and topically safe in chronic pain conditions. However, further study will be required with larger sample size and in heterogeneous population to elicit long-term effect of this polyherbal preparation.