Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer's Disease Therapy.

Alzheimer's disease (AD) is a gradually growing irreversible illness of the brain that almost affects every fifth person (aged > 80 years) in the world. World Health Organization (WHO) also revealed that the prevalence of this disease will enhance (upto double) significantly upto 2030. The poor cholinergic transmission at the synapse is considered to be one of the main reasons behind the progression and occurrence of this disorder. Natural inhibitors of acetylcholine (ACh) such as galanthamine and rivastigmine are used commercially in the treatmentof AD. The biomolecules such assesquiterpenes, possess a great structural diversity and are responsible for a plethora of pharmacological properties. The potential of various sesquiterpenes as anticholinesterase has been reviewed in this article. For this purpose, the various databases, mainly PubMed, Scopus, and Web of Science were investigatedwith different keywords such as "sesquiterpenes+acetylcholinesterase" and "sesquiterpenes+cholinesterase+inhibitors" in the surveyed time frame (2010-2020). A vast literature was evident in the last decade, which affirms the potential of various sesquiterpenes in the improvement of cholinergic transmission by inhibiting the AChE. After data analysis, it was found that 12 compounds out of a total of 58 sesquiterpenes were reported to possess IC50 < 9µM and can be considered as potential candidates for the improvement of learning and memory. Sesquiterpene is an important category of terpenoids, found to possess a large spectrum of biological activities. The outcome of the review clearly states that sesquiterpenes (such as amberboin, lipidiol,etc) from herbs could offer fresh, functional compounds for possible prevention and treatment of AD.

Ecofriendly Ethyl Cellulose Microsponges of Citronella Oil: Preparation, Characterization and Evaluation of Cytotoxicity and Larvicidal assay.

BACKGROUND: Citronella Oil (CO) was used by the Indian army as mosquito repellant to repel mosquitoes at the beginning of the 20th century and later in 1948, it was registered in the USA for commercial purposes. Due to its ecofriendly nature, CO possesses immense potential as a mosquito repellent. METHODS: Citronella oil is a valuable alternative to synthetic mosquito repellents commonly used nowadays. However, its volatile nature, poor stability in air and high temperature restrict its application. Its direct application on skin may lead to skin irritation. To surmount the above-mentioned issues, the present research aims to develop Microsponge (MS), a novel dosage form for enhancing the utility and safety of CO. Quasi emulsion solvent diffusion method was chosen for crafting MS using ethyl cellulose with various drug-polymer ratios and characterized. In vitro cytotoxicity evaluation was also carried out to check the dermal safety of COMS. RESULTS: The present results revealed that the size of all prepared formulation lies in the micro range (20 ± 3 to 41 ± 4 µm), with good payload (42.09± 3.24 to 67.08± 6.43%). The results of FE-SEM depicted that MS were spherical in shape with porous nature. Cytotoxicity results indicated that COMS were safe on skin cells, when compared to pure CO. The optimized MS were also assessed for larvicidal assay against larvae of Anopheles culicifacies. CONCLUSION: The CO micro-formulations were found to possess enhanced stability of this oil. Entrapment of CO in MS resulted in a better vehicle system in terms of safety, stability and handling benefits of this oil.

Enhanced anti-psoriatic efficacy and regulation of oxidative stress of a novel topical babchi oil (Psoralea corylifolia) cyclodextrin-based nanogel in a mouse tail model.

Psoriasis is a proliferative inflammatory skin disorder with relapsing episodes. Herein, the efficacy of babchi oil (BO) loaded nanostructure gel was evaluated for antipsoriatic activity and oxidative stress biomarkers assessment using mouse tail model. BO was entrapped into cyclodextrin-based nanocarriers (360.9 ± 19.55 nm), followed by incorporation into Carbopol gel and characterised for viscosity, spreadability, and texture analysis. The gels were topically applied on mouse-tails once daily for fourteen days. Evaluation of antipsoriatic activity as determined by histopathological observations of orthokeratotic epidermis revealed two times higher efficacy of BO nanogel in comparison to the native BO gel. Further, significantly enhanced superoxide dismutase (SOD) and reduced glutathione (GSH) levels, and diminished malondialdehyde (MDA) and nitrite (NO) levels revealed that prepared nanogels played a major role in the management of reactive oxygen species (ROS) associated in psoriasis pathogenesis. Hence, this study provides strong evidence for use of cyclodextrin-based nanogels as a safe and better delivery carrier of BO for management of psoriasis.

Encapsulation of babchi essential oil into microsponges: Physicochemical properties, cytotoxic evaluation and anti-microbial activity.

Babchi essential oil (BEO) is a valuable essential oil reported to possess a variety of biological activities such as antitumor, anti inflammatory, immunomodulatory, antioxidant, antifungal and antibacterial properties. Due to its anti-microbial properties, this oil possesses an immense potential for the treatment of dermatological disorders. Further, it has minimal tendency to develop resistance, a common issue with most of the antibiotics. However, its highly viscous nature and poor stability in the presence of light, air and high temperature, limits its practical applications. To surmount these issues, this research aims to encapsulate BEO in ethyl cellulose (EC) microsponges for enhanced stability, antibacterial effect and decreased dermal toxicity. The quasi emulsion solvent evaporation technique was used for fabrication of the BEO microsponges employing EC as polymer, polyvinyl alcohol (PVA) as stabilizer and dichloro methane (DCM) as solvent. The effect of formulation variables such as the amount of EC and PVA were also investigated. The prepared microformulations were evaluated for production yield, encapsulation efficiency, particle size and in vitro release. In vitro cytotoxicity was also checked to assess dermal safety of BEO microsponges. Results revealed that all the dispersions were in micro size range (20.44 ± 3.13 µm to 41.75 ± 3.65 µm), with good encapsulation efficiency (87.70 ± 1.20% of F2) and controlled release profile (cumulative drug release 73.34 ± 1.76%). Field emission scanning electron microscopy results showed that the microsponges possessed a spherical uniform shape with a spongy structure. Results of cytotoxicity study indicated that the prepared microsponges were safer on dermal cells in comparison to pure BEO. The optimized formulation was also evaluated for in vitro antimicrobial assay against dermal bacteria like Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, which confirmed their enhanced antibacterial activity. Furthermore, the results of photostability and stability analysis indicated improved stability of BEO loaded microsponges. Hence, encapsulation of BEO in microsponges resulted in efficacious carrier system in terms of stability as well as safety of this essential oil alongwith handling benefits.

Therapeutic Potential of Citronella Essential Oil: A Review.

Mosquito-borne diseases such as malaria, filariasis, chikunguniya, yellow fever, dengue and Japanese encephalitis are the major cause of remarkable morbidity and mortality in livestock and humans worldwide. Since ancient times, aromatic plants are used for their medicinal value. Essential oils derived from these plants may be used as effective alternatives/adjuvants in pharmaceuticals, biomedical, cosmetic, food, veterinary and agriculture applications. These oils have also gained popularity and interest for prevention and treatment of various disorders. However, several reports on adverse effects including skin eruption, contact artricaria or toxic encephalopathy in children are available for synthetic repellent in the literature. Thus, natural insect repellents like essential oils have been explored recently as an alternative. One such essential oil studied widely, is citronella oil, extracted mainly from Cymbopogon nardus. This essential oil has exhibited good efficacy against mosquitoes. It is a mixture of components including citronellal, citronellol, geraniol as major constituents contributing to various activities (antimicrobial, anthelmintic, antioxidant, anticonvulsant antitrypanosomal and wound healing), besides mosquito repellent action. Citronella essential oil is registered in US EPA (Environmental protection agency) as insect repellent due to its high efficacy, low toxicity and customer satisfaction. However, poor stability in the presence of air and high temperature limits its practical applications. Since specific knowledge on properties and chemical composition of oil is fundamental for its effective application, the present review compiles and discusses biological properties of citronella oil. It also sheds light on various formulations and applications of this essential oil.

Encapsulation of Babchi Oil in Cyclodextrin-Based Nanosponges: Physicochemical Characterization, Photodegradation, and In Vitro Cytotoxicity Studies.

Babchi (Psoralea corylifolia) oil is an important essential oil used in several traditional medicines to cure various disorders. This phytotherapeutic agent possesses a number of pharmacological activities including antibacterial, antifungal, antioxidant, anti-inflammatory, immunomodulatory, and antitumor factors. However, volatile nature, poor stability, and solubility of babchi oil (BO) restrict its pharmaceutical applications. Therefore, the aim of the present work was to encapsulate this oil in ß-cyclodextrin nanosponges (NS) in order to overcome the above limitations. To fabricate nanosponges, ß-cyclodextrin was cross-linked with diphenyl carbonate in different molar ratios viz. 1:2, 1:4, 1:6, 1:8, and 1:10. The blank nanosponges were loaded with BO using the freeze-drying method. The particle size of the BO loaded nanosponges was found to lie between 200 and 500 nm with low polydispersity index. Furthermore, the zeta potential, the Fourier transform infrared spectroscopy, X-ray diffraction, thermal analysis, and electron microscopy were carried out for characterization of BO nanosponges. Results obtained from spectral analysis ascertained the formation of inclusion complexes. Additionally, solubilisation efficiency of BO was checked in distilled water and found enhanced by 4.95 times with optimized ß-cyclodextrin nanosponges. The cytotoxicity study was carried out by the MTT assay using HaCaT cell lines. A significant improvement in photo-stability of essential oil was also observed by inclusion innanosponges. Lastly, the optimized formulation was tested for antibacterial activity using Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Therefore, encapsulation of BO in nanosponges resulted in efficacious carrier system in terms of solubility, photo-stability, and safety of this oil along with handling benefits.

Novel Carriers for Coenzyme Q10 Delivery.

BACKGROUND: Coenzyme Q10, a natural yellow benzoquinone, is a vitamin-like substance commonly found in blood and inner mitochondrial and cellular membranes. It is a natural antioxidant principle which plays an essential role in maintaining several biochemical pathways of body. It has exhibited many pharmacological activities in chronic heart failure, cardiofaciocutaneous syndrome, diabetes mellitus, carcinomas, autoimmune disease, cataract, asthma, periodontal disease and thyroid disorders. Moreover, it has demonstrated efficacy as nutritional supplement, in addition to its relevance in cosmetics. OBJECTIVE: Coenzyme Q10 is a potent molecule but its high molecular weight and low aqueous solubility hamper its use as a therapeutic agent. Therefore, various novel drug delivery systems have been explored and developed to overcome these limitations in literature. Hence, objective of this review is to summarize the recent works on design and development of novel drug delivery systems for CoQ10, which include liposomes, polymeric nanoparticles, polymeric micelles, solid lipid nanoparticles, nanostructured lipid carriers, self-emulsifying drug delivery systems, nanoemulsions, solid and aqueous dispersions. Further, an account of pharmaceutical studies has also been given. RESULTS & CONCLUSION: The reported studies indicate the promise of nanotechnology in enhancing the therapeutic value of CoQ10, promoting its usage as first line therapeutic agent, thus, revolutionizing its role in current medical therapy. The application of CoQ10 in pharmaceutical industry has grown tremendously in the past decade, due to its versatile nature. The successful application of this molecule in medicine, cosmetics and nutraceuticals points the way for its future development.

Combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A and the histone deacetylase inhibitor panobinostat against human AML cells.

The polycomb repressive complex (PRC) 2 contains 3 core proteins, EZH2, SUZ12, and EED, in which the SET (suppressor of variegation-enhancer of zeste-trithorax) domain of EZH2 mediates the histone methyltransferase activity. This induces trimethylation of lysine 27 on histone H3, regulates the expression of HOX genes, and promotes proliferation and aggressiveness of neoplastic cells. In this study, we demonstrate that treatment with the S-adenosylhomocysteine hydrolase inhibitor 3-deazaneplanocin A (DZNep) depletes EZH2 levels, and inhibits trimethylation of lysine 27 on histone H3 in the cultured human acute myeloid leukemia (AML) HL-60 and OCI-AML3 cells and in primary AML cells. DZNep treatment induced p16, p21, p27, and FBXO32 while depleting cyclin E and HOXA9 levels. Similar findings were observed after treatment with small interfering RNA to EZH2. In addition, DZNep treatment induced apoptosis in cultured and primary AML cells. Furthermore, compared with treatment with each agent alone, cotreatment with DZNep and the pan-histone deacetylase inhibitor panobinostat caused more depletion of EZH2, induced more apoptosis of AML, but not normal CD34(+) bone marrow progenitor cells, and significantly improved survival of nonobese diabetic/severe combined immunodeficiency mice with HL-60 leukemia. These findings indicate that the combination of DZNep and panobinostat is effective and relatively selective epigenetic therapy against AML cells.