Nigella sativa Oil-loaded Ethanolic Vesicular Gel for Imiquimod-induced Plaque Psoriasis: Physicochemical Characterization, Rheological Studies, and In vivo Efficacy.

BACKGROUND: The therapeutic effect of NS oil in mild to moderate psoriasis is limited owing to low play load of thymoquinone ( < 15 %w/w), irritation, dripping, low viscosity and thus, less contact time on the lesions. AIMS: This study aimed at developing and characterizing the ethanolic vesicular hydrogel system of Nigella sativa (NS) oil (NS EV hydrogel) for the enhancement of anti-psoriatic activity. OBJECTIVE: The objective of this study was to develop NS EV hydrogel and evaluate its anti-psoriatic activity. METHODS: The identification and quantification of TQ content in different NS seed extracts and marketed oil were measured by an HPTLC method using n-hexane and ethyl acetate as solvent systems. Preparation of ethanolic vesicles (EVs) was performed by solvent injection method, while its antipsoriatic activity was evaluated employing an Imiquad (IMQ)-induced plaque psoriasis animal model. RESULTS: A compact HPTLC band was obtained for TQ at an Rf value of 0.651. The calibration plot was linear in the range of 1-10 µg/spot, and the correlation coefficient of 0.990 was indicative of good linear dependence of peak area on concentration. From the different NS sources, the high TQ content was obtained in the marketed cold press oil, i.e., 1.45±0.08mg/ml. Out of various NS oilloaded EVs, the F6 formulation revealed the smallest particle size (278.1nm), with log-normal size distribution (0.459) and adequate entrapment efficiency. A non-uniform shape was observed in the transmission electron microscopy. The viscosity of F6 formulation hydrogel was 32.34 (Pa·s), which exhibited plastic behavior. In vivo, efficacy studies demonstrated decreased inflammation of the epidermis and dermis and a marked decrease in the levels of IL-17 by NS EV hydrogel compared to plain NS oil and standard drugs (Betamethasone and Dr. JRK Psorolin Oil). CONCLUSION: It may be concluded from the findings that NS-loaded EV gel was as good as betamethasone cream but more efficacious than the other treatments.

From nature's bounty to drug discovery: Leveraging phytochemicals and molecular approaches to combat multi-drug-resistant (MDR) tuberculosis.

A large number of people annually lose their lives to tuberculosis (TB), which is an age-old disease caused by the Mycobacterium tuberculosis. The global spread of TB is a concern for all regions. The south-east Asian region recorded 46% of all new TB cases in 2021, followed by the African and western Pacific regions with 23% and 18%, respectively. Researchers are always searching at natural substances for potential alternative therapeutics to tackle the worrisome growth in multi-drug-resistant (MDR) tuberculosis due to the high costs associated with developing new treatments and unfavourable side effects of currently used synthetic pharmaceuticals. Phytochemicals show promising results as a future health aid due to their multi-targeting ability on pathogen cells. In the search for new drug leads, the Ayurvedic and Siddha medical systems have made an extensive use of ethnomedicinal tools, including the use of plants like Amalaki (Emblica officinalis Gaertn.), Guduchi (Tinospora cordifolia willd.), Sariva (Hemidesmus indicus R.Br.), Kustha (Saussurea lappa Falc.), turmeric (Curcuma longa Mal.) and Green tea (Camellia sinensis Linn.). These sources are high in flavonoids, polyphenols, tannins and catechins, has been shown to reduce the risk of TB. In this overview, we look at how natural sources like plants, algae and mushrooms have helped researchers to find new drug leads, and how to back these natural sources through mapping the molecular approaches and other approaches has helped them to defeat MDR.

Polymeric micelles as potent islet amyloid inhibitors: Current advances and future perspectives.

Diabetes mellitus (DM) has become one of the most prevalent diseases across the globe, mainly because of the inability of existing treatment strategies to target its root cause (i.e., pancreatic ß cell damage). Polymeric micelles (PMs) have gained attention as a treatment option for DM by targeting misfolded islet amyloid polypeptide protein (IAPP), which is common in more than 90% of DM patients. Such misfolding could result from either oxidative stress or mutation in the gene encoding IAPP. In this review, we discuss progress in the designing of PMs to halt islet amyloidosis along with their mechanism and dynamics of interactions with IAPP. We also discuss the clinical challenges associated with the translation of PMs as anti-islet amyloidogenic agents.

The FBXW7-NOTCH interactome: A ubiquitin proteasomal system-induced crosstalk modulating oncogenic transformation in human tissues.

BACKGROUND: Ubiquitin ligases or E3 ligases are well programmed to regulate molecular interactions that operate at a post-translational level. Skp, Cullin, F-box containing complex (or SCF complex) is a multidomain E3 ligase known to mediate the degradation of a wide range of proteins through the proteasomal pathway. The three-dimensional domain architecture of SCF family proteins suggests that it operates through a novel and adaptable "super-enzymatic" process that might respond to targeted therapeutic modalities in cancer. RECENT FINDINGS: Several F-box containing proteins have been characterized either as tumor suppressors (FBXW8, FBXL3, FBXW8, FBXL3, FBXO1, FBXO4, and FBXO18) or as oncogenes (FBXO5, FBXO9, and SKP2). Besides, F-box members like ßTrcP1 and ßTrcP2, the ones with context-dependent functionality, have also been studied and reported. FBXW7 is a well-studied F-box protein and is a tumor suppressor. FBXW7 regulates the activity of a range of substrates, such as c-Myc, cyclin E, mTOR, c-Jun, NOTCH, myeloid cell leukemia sequence-1 (MCL1), AURKA, NOTCH through the well-known ubiquitin-proteasome system (UPS)-mediated degradation pathway. NOTCH signaling is a primitive pathway that plays a crucial role in maintaining normal tissue homeostasis. FBXW7 regulates NOTCH protein activity by controlling its half-life, thereby maintaining optimum protein levels in tissue. However, aberrations in the FBXW7 or NOTCH expression levels can lead to poor prognosis and detrimental outcomes in patients. Therefore, the FBXW7-NOTCH axis has been a subject of intense study and research over the years, especially around the interactome's role in driving cancer development and progression. Several studies have reported the effect of FBXW7 and NOTCH mutations on normal tissue behavior. The current review attempts to critically analyze these mutations prognostic value in a wide range of tumors. Furthermore, the review summarizes the recent findings pertaining to the FBXW7 and NOTCH interactome and its involvement in phosphorylation-related events, cell cycle, proliferation, apoptosis, and metastasis. CONCLUSION: The review concludes by positioning FBXW7 as an effective diagnostic marker in tumors and by listing out recent advancements made in cancer therapeutics in identifying protocols targeting the FBXW7-NOTCH aberrations in tumors.