Probing the anti-Aß42 aggregation and protective effects of prenylated xanthone against Aß42-induced toxicity in transgenic Caenorhabditis elegans model.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-ß (Aß) protein aggregates, leading to synaptic dysfunction and neuronal cell death. In this study, we used a comprehensive approach encompassing in vitro assays, computational analyses, and an in vivo Caenorhabditis elegans model to evaluate the inhibitory effects of various xanthones, focusing on Garcinone D (GD), on Aß42 oligomer formation. Dot blot analysis revealed concentration-dependent responses among xanthones, with GD consistently inhibiting Aß42 oligomer formation at low concentrations (0.1 and 0.5 µM, inhibitions of 84.66 ± 2.25% and 85.06 ± 6.57%, respectively). Molecular docking and dynamics simulations provided insights into the molecular interactions between xanthones and Aß42, highlighting the disruption of key residues involved in Aß42 aggregation. The neuroprotective potential of GD was established using transgenic C. elegans GMC101, with substantial delays in paralysis reported at higher concentrations. Our findings show that GD is a potent suppressor of Aß42 oligomer formation, suggesting its potential as a therapeutic candidate for AD. The concentration-dependent effects observed in both in vitro and in vivo models underscore the need for nuanced dose-response assessments. These findings contribute novel insights into the therapeutic landscape of xanthones against AD, emphasizing the multifaceted potential of GD for further translational endeavors in neurodegenerative disorder research.

Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases.

The human gastrointestinal tract is populated with a diverse microbial community. The vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect of human biology, including health maintenance, development, aging, and disease. The advent of new sequencing technologies and culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations to shed light on microbiome-host interactions. Evidence has unveiled the bidirectional communication between the gut microbiome and the central nervous system, referred to as the "microbiota-gut-brain axis". The microbiota-gut-brain axis represents an important regulator of glial functions, making it an actionable target to ameliorate the development and progression of neurodegenerative diseases. In this review, we discuss the mechanisms of the microbiota-gut-brain axis in neurodegenerative diseases. As the gut microbiome provides essential cues to microglia, astrocytes, and oligodendrocytes, we examine the communications between gut microbiota and these glial cells during healthy states and neurodegenerative diseases. Subsequently, we discuss the mechanisms of the microbiota-gut-brain axis in neurodegenerative diseases using a metabolite-centric approach, while also examining the role of gut microbiota-related neurotransmitters and gut hormones. Next, we examine the potential of targeting the intestinal barrier, blood-brain barrier, meninges, and peripheral immune system to counteract glial dysfunction in neurodegeneration. Finally, we conclude by assessing the pre-clinical and clinical evidence of probiotics, prebiotics, and fecal microbiota transplantation in neurodegenerative diseases. A thorough comprehension of the microbiota-gut-brain axis will foster the development of effective therapeutic interventions for the management of neurodegenerative diseases.

Hydroxychloroquine: Key therapeutic advances and emerging nanotechnological landscape for cancer mitigation.

Hydroxychloroquine (HCQ) is a unique class of medications that has been widely utilized for the treatment of cancer. HCQ plays a dichotomous role by inhibiting autophagy induced by the tumor microenvironment (TME). Preclinical studies support the use of HCQ for anti-cancer therapy, especially in combination with conventional anti-cancer treatments since they sensitize tumor cells to drugs, potentiating the therapeutic activity. However, clinical evidence has suggested poor outcomes for HCQ due to various obstacles, including non-specific distribution, low aqueous solubility and low bioavailability at target sites, transport across tissue barriers, and retinal toxicity. These issues are addressable via the integration of HCQ with nanotechnology to produce HCQ-conjugated nanomedicines. This review aims to discuss the pharmacodynamic, pharmacokinetic and antitumor properties of HCQ. Furthermore, the antitumor performance of the nanoformulated HCQ is also reviewed thoroughly, aiming to serve as a guide for the HCQ-based enhanced treatment of cancers. The nanoencapsulation or nanoconjugation of HCQ with nanoassemblies appears to be a promising method for reducing the toxicity and improving the antitumor efficacy of HCQ.

Emerging Nanotheranostics for 5-Fluorouracil in Cancer Therapy: A Systematic Review on Efficacy, Safety, and Diagnostic Capability.

The conventional concept of using nanocarriers to deliver chemotherapeutic drugs has advanced to accommodate additional diagnostic capability. Nanotheranostic agents (NTA), combining both treatment and diagnostic tools, are an ideal example of engineering-health integration for cancer management. Owing to the diverse materials used to construct NTAs, their safety, effectiveness, and diagnostic accuracy could vary substantially. This systematic review consolidated current NTAs incorporating 5-fluorouracil and elucidated their toxicity, anticancer efficacy, and imaging capability. Medline and Embase databases were searched up to March 18, 2022. The search, selection, and extraction were performed by the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines to ensure completeness and reproducibility. Original research papers involving 5-fluorouracil in the preparation of nanoparticles which reported their efficacy, toxicity, and diagnostic capability in animal cancer models were recruited. The quality of included studies was assessed using the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist. Nine studies were eligible for the systematic review. There was no significant toxicity reported based on animal weight and organ histology. Complete tumor remission was observed in several animal models using chemo-thermal ablation with NTAs, proving the enhancement of 5-fluorouracil efficacy. In terms of imaging performance, the time to achieve maximum tumor image intensity correlates with the presence of targeting ligand on NTAs. The NTAs, which are composed of tumor-targeting ligands, hold promises for further development. Based on the input of current NTA research on cancer, this review proposed a checklist of parameters to recommend researchers for their future NTA testing, especially in animal cancer studies. Systematic Review Registration: website, identifier registration number.

Natural HSP90 inhibitors as a potential therapeutic intervention in treating cancers: A comprehensive review.

Heat shock protein 90 (Hsp90) has evolved as a cancerous cell growth regulator by stabilising various oncogenic kinases. Upon the Hsp90 inhibition, the expression of its client proteins is downregulated and thus leads to denaturation of cellular proteins and cancer cell death. Hsp90 inhibitors, particularly those naturally derived from plants, fungi and bacteria, have gained substantial interest as a feasible therapeutic approach for cancer treatment due to their diverse pharmacological properties. In order to gain insights into the potential development of more efficacious Hsp90 inhibitors for cancer treatment, this review is conducted to analyse both in vitro and in vivo data on the chemical and biological activities of natural Hsp90 inhibitors. The systematic search was conducted in databases (PubMed, Scopus and Web of Science) with terms "Hsp90 inhibitor" and "cancer", prompting a total of 61 articles after screening with inclusion criteria. This comprehensive review systematically summarised the efficacy of 14 different classes of naturally derived Hsp90 inhibitors in cancerous cell and animal tumour models by consolidating the primary outcomes in terms of IC50, reduction of tumour size and physicochemical properties. The detailed pharmacodynamic (the structure-activity relationship, mechanism of action) and pharmacokinetics (toxicity, oral bioavailability) of these Hsp90 inhibitors together with the study limitations were discussed. Collectively, these findings emphasise the necessity of comprehending the molecular mechanisms as well as the correlation of Hsp90 and its relative client proteins to drive the generation of viable Hsp90 inhibitors with improved pharmacodynamic and pharmacokinetic profiles.

Stimuli-controllable iron oxide nanoparticle assemblies: Design, manipulation and bio-applications.

Despite its wide establishment over the years, iron oxide nanoparticle (IONP) still draws extensive interest in the biomedical fields due to its biocompatibility, biodegradability, magnetivity and surface tunable properties. IONP has been used for the MRI, magnetic targeting, drug delivery and hyperthermia of various diseases. However, their poor stability, low diagnostic sensitivity and low disease-specificity have resulted in unsatisfying diagnostic and therapeutic outputs. The surface functionalization of IONP with biocompatible and colloidally stable components appears to be promising to improve its circulation and colloidal stability. Importantly, through surface functionalization with designated functional components, IONP-based assemblies with multiple stimuli-responsivity could be formed to achieve an accurate and efficient delivery of IONP to disease sites for an improved disease diagnosis and therapy. In this work, we first described the design of biocompatible and stable IONP assemblies. Further, their stimuli-driven manipulation strategies are reviewed. Next, the utilization of IONP assemblies for disease diagnosis, therapy and imaging-guided therapy are discussed. Then, the potential toxicity of IONPs and their clinical usages are described. Finally, the intrinsic challenges and future outlooks of IONP assemblies are commented. This review provides recent insights into IONP assemblies, which could inspire researchers on the future development of multi-responsive and disease-targetable nanoassemblies for biomedical utilization.

How far have we explored fungi to fight cancer?

The use of fungal cultures have been well documented in human history. Although its used in healthcare, like penicillin and statins, have saved countless of lives, but there is still no fungal products that are specifically indicated for cancers. Research into fungal-derived materials to curb cancers in the recent decades have made a considerable progress in terms of drug delivery vehicles, anticancer active ingredients and cancer immunotherapy. Various parts of the organisms have successfully been exploited to achieve specific tasks. Apart from the identification of novel anticancer compound from fungi, its native capsular structure can also be used as drug cargo to achieve higher oral bioavailability. This review summarises the anticancer potential of fungal-derived materials, highlighting the role of capsular polysaccharides, proteins, and other structures in variety of innovative utilities to fit the current pharmaceutical technology. Many bioactive compounds isolated from fungi have also been formulated into nanoparticles to achieve greater anticancer activity. The progress of fungal compounds and their analogues in clinical trials is also highlighted. In addition, the potential of various fungal species to be developed for anticancer immunotherapy are also discussed.

Induction of Apoptosis and Autophagy by Ternary Copper Complex Towards Breast Cancer Cells.

BACKGROUND: Copper complex has been gaining much attention in anticancer research as a targeted agent since cancer cells uptake more copper than non-cancerous cells. Our group synthesised a ternary copper complex, which is composed of 1,10-phenanthroline and tyrosine [Cu(phen)(L-tyr)Cl].3H20. These two payloads have been designed to cleave DNA and inhibit protein degradation system (proteasome) concurrently in cancer cells, making this copper complex a dual-target compound. OBJECTIVE: The current study was carried out to investigate the mode of cell death and the role of autophagy induced by [Cu(phen)(L-tyr)Cl].3H20 in MCF-7 and MDA-MB-231 breast cancer cells. METHODS: Growth inhibition of [Cu(phen)(L-tyr)Cl].3H20 towards MDA-MB-231 and human non-cancerous MCF10A breast cells was determined by MTT assay. Annexin-V-FITC/PI and cell cycle analysis were evaluated by flow cytometry. The expression of p53, Bax, caspase-9, caspase-7, caspase-3 and LC3 was determined using western blot analysis. The cells were then co-treated with hydroxychloroquine to ascertain the role of autophagy induced by [Cu(phen)(L-tyr)Cl].3H20. RESULTS: [Cu(phen)(L-tyr)Cl].3H20 inhibited the growth of cancer cells dose-dependently with less toxicity towards MCF10A cells. Additionally, [Cu(phen)(L-tyr)Cl].3H20 induced apoptosis and cell cycle arrest towards MCF-7 and MDA-MB-231 breast cancer cells possibly via regulation of p53, Bax, caspase-9, caspase-3 and capase-7. The expression of LC3II was upregulated in both cancer cell lines upon treatment with [Cu(phen)(L-tyr) Cl].3H20, indicating the induction of autophagy. Co-treatment with autophagy inhibitor hydroxychloroquine significantly enhanced growth inhibition of both cell lines, suggesting that autophagy induced by [Cu(phen)(L-tyr) Cl].3H20 in both breast cancer cells promoted cell survival. CONCLUSION: [Cu(phen)(L-tyr)Cl].3H20 holds great potential to be developed for breast cancer treatment.

Do Lipid-based Nanoparticles Hold Promise for Advancing the Clinical Translation of Anticancer Alkaloids?

Since the commercialization of morphine in 1826, numerous alkaloids have been isolated and exploited effectively for the betterment of mankind, including cancer treatment. However, the commercialization of alkaloids as anticancer agents has generally been limited by serious side effects due to their lack of specificity to cancer cells, indiscriminate tissue distribution and toxic formulation excipients. Lipid-based nanoparticles represent the most effective drug delivery system concerning clinical translation owing to their unique, appealing characteristics for drug delivery. To the extent of our knowledge, this is the first review to compile in vitro and in vivo evidence of encapsulating anticancer alkaloids in lipid-based nanoparticles. Alkaloids encapsulated in lipid-based nanoparticles have generally displayed enhanced in vitro cytotoxicity and an improved in vivo efficacy and toxicity profile than free alkaloids in various cancers. Encapsulated alkaloids also demonstrated the ability to overcome multidrug resistance in vitro and in vivo. These findings support the broad application of lipid-based nanoparticles to encapsulate anticancer alkaloids and facilitate their clinical translation. The review then discusses several limitations of the studies analyzed, particularly the discrepancies in reporting the pharmacokinetics, biodistribution and toxicity data. Finally, we conclude with examples of clinically successful encapsulated alkaloids that have received regulatory approval and are undergoing clinical evaluation.

Unraveling the Immunopathogenesis and Genetic Variants in Vasculitis Toward Development of Personalized Medicine.

Leukocytoclastic vasculitis (LCV) is a systemic autoimmune disease characterized by the inflammation of the vascular endothelium. Cutaneous small vessel vasculitis (CSVV) and anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) are two examples of LCV. Advancements in genomic technologies have identified risk haplotypes, genetic variants, susceptibility loci and pathways that are associated with vasculitis immunopathogenesis. The discovery of these genetic factors and their corresponding cellular signaling aberrations have enabled the development and use of novel therapeutic strategies for vasculitis. Personalized medicine aims to provide targeted therapies to individuals who show poor response to conventional interventions. For example, monoclonal antibody therapies have shown remarkable efficacy in achieving disease remission. Here, we discuss pathways involved in disease pathogenesis and the underlying genetic associations in different populations worldwide. Understanding the immunopathogenic pathways in vasculitis and identifying associated genetic variations will facilitate the development of novel and targeted personalized therapies for patients.

Streptomyces sp.-A Treasure Trove of Weapons to Combat Methicillin-Resistant Staphylococcus aureus Biofilm Associated with Biomedical Devices.

Biofilms formed by methicillin-resistant S. aureus (MRSA) are among the most frequent causes of biomedical device-related infection, which are difficult to treat and are often persistent and recurrent. Thus, new and effective antibiofilm agents are urgently needed. In this article, we review the most relevant literature of the recent years reporting on promising anti-MRSA biofilm agents derived from the genus Streptomyces bacteria, and discuss the potential contribution of these newly reported antibiofilm compounds to the current strategies in preventing biofilm formation and eradicating pre-existing biofilms of the clinically important pathogen MRSA. Many efforts are evidenced to address biofilm-related infections, and some novel strategies have been developed and demonstrated encouraging results in preclinical studies. Nevertheless, more in vivo studies with appropriate biofilm models and well-designed multicenter clinical trials are needed to assess the prospects of these strategies.

Anticancer activities of dietary benzyl isothiocyanate: A comprehensive review.

Benzyl isothiocyanate (BITC) is one of the common isothiocyanates found in cruciferous vegetables such as broccoli, cabbage or watercress. Preclinical studies report of its effectiveness in the prevention and treatment against several cancers. This review aims to report and discuss findings on anticancer activities of BITC and its modes of action against 14 types of cancer. A literature search was conducted using the keywords "BITC" and "anticancer" from PubMed, Google Scholar and CINAHL Plus to obtain relevant research articles. This review highlights the anticancer efficacy of BITC through modulation of various signaling pathways involved in apoptosis, cell proliferation, cell cycle arrest, metastasis, angiogenesis, autophagy and the effects of BITC in combination with other drugs. With the available pharmacology evidence, we conclude that further studies are needed to validate its effectiveness in humans for further development and translation into prophylaxis or therapy by promoting optimal therapeutic effects and minimizing toxicity in cancer treatment.

Beneficial Role of Carica papaya Extracts and Phytochemicals on Oxidative Stress and Related Diseases: A Mini Review.

Oxidative stress is a result of disruption in the balance between antioxidants and pro-oxidants in which subsequently impacting on redox signaling, causing cell and tissue damages. It leads to a range of medical conditions including inflammation, skin aging, impaired wound healing, chronic diseases and cancers but these conditions can be managed properly with the aid of antioxidants. This review features various studies to provide an overview on how Carica papaya help counteract oxidative stress via various mechanisms of action closely related to its antioxidant properties and eventually improving the management of various oxidative stress-related health conditions. Carica papaya is a topical plant species discovered to contain high amounts of natural antioxidants that can usually be found in their leaves, fruits and seeds. It contains various chemical compounds demonstrate significant antioxidant properties including caffeic acid, myricetin, rutin, quercetin, α-tocopherol, papain, benzyl isothiocyanate (BiTC), and kaempferol. Therefore, it can counteract pro-oxidants via a number of signaling pathways that either promote the expression of antioxidant enzymes or reduce ROS production. These signaling pathways activate the antioxidant defense mechanisms that protect the body against both intrinsic and extrinsic oxidative stress. To conclude, Carica papaya can be incorporated into medications or supplements to help manage the health conditions driven by oxidative stress and further studies are needed to investigate the potential of its chemical components to manage various chronic diseases.

Licorice: A Potential Herb in Overcoming SARS-CoV-2 Infections.

The management of the global pandemic outbreak due to the coronavirus disease (COVID-19) has been challenging with no exact dedicated treatment nor established vaccines at the beginning of the pandemic. Nonetheless, the situation seems to be better controlled with the recent COVID-19 vaccines roll-out globally as active immunisation to prevent COVID-19. The extensive usage and trials done in recent outbreak in China has shown the effectiveness of traditional Chinese Medicines (TCM) in improving the wellbeing of COVID-19 patients. Therefore, COVID-19 Prevention and Treatment guidelines has listed a number of recommended concoctions meant for COVID-19 patients. Licorice, more commonly known as Gancao in Chinese Pinyin, is known as one of the most frequently used ingredients in TCM prescriptions for treatment of epidemic diseases. Interestingly, it is deemed as food ingredient as well, where it is normally used in Western cuisines' desserts and sweets. The surprising fact that licorice appeared in the top 10 main ingredients used in TCM prescriptions in COVID-19 has drawn great attention from researchers in revealing its biological potential in overcoming this disease. To date, there are no comprehensive review on licorice and its benefits when used in COVID-19. Thus, in this current review, the possible benefits, mechanism of actions, safety and limitations of licorice were explored in hope to provide a quick reference guide for its preclinical and clinical experimental set-up in this very critical moment of pandemic.

Focused Review: Potential Rare and Atypical Symptoms as Indicator for Targeted COVID-19 Screening.

The global pandemic of the coronavirus disease 2019 is a known consequence of infection of severe respiratory syndrome coronavirus-2 (SARS-CoV-2). It has affected nations worldwide with soaring number of cases daily. Symptoms such as fever, cough, and shortness of breath, diarrhea, nausea and vomiting are commonly presented in COVID-19 patients. This focused review aims to discuss these uncommon and atypical COVID-19 symptoms that may be presented which might affect neurological, cardiovascular, cutaneous and ocular systems and their possible mode of actions. Nonetheless, there are some cases of reported uncommon or atypical symptoms which may warrant healthcare professionals to be aware of, especially when in contact with patients. The knowledge and information concerning these symptoms might be able to provide additional cues for healthcare professional by subjecting patients to COVID-19 screening. Meanwhile, it might be able to further enhance the alertness and additional precautions being taken by healthcare personnel, which eventually lead to reduced risk of infections.

Pharmacokinetics and Biodistribution of Thymoquinone-loaded Nanostructured Lipid Carrier After Oral and Intravenous Administration into Rats.

BACKGROUND: Thymoquinone (TQ), an active compound isolated from Nigella sativa, has been proven to exhibit various biological properties such as antioxidant. Although oral delivery of TQ is valuable, it is limited by poor oral bioavailability and low solubility. Recently, TQ-loaded nanostructured lipid carrier (TQ-NLC) was formulated with the aim of overcoming the limitations. TQ-NLC was successfully synthesized by the high-pressure homogenization method with remarkable physiochemical properties whereby the particle size is less than 100 nm, improved encapsulation efficiency and is stable up to 24 months of storage. Nevertheless, the pharmacokinetics and biodistribution of TQ-NLC have not been studied. This study determined the bioavailability of oral and intravenous administration of thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) in rats and its distribution to organs. MATERIALS AND METHODS: TQ-NLC was radiolabeled with technetium-99m before the administration to the rats. The biodistribution and pharmacokinetics parameters were then evaluated at various time points. The rats were imaged at time intervals and the percentage of the injected dose/gram (%ID/g) in blood and each organ was analyzed. RESULTS: Oral administration of TQ-NLC exhibited greater relative bioavailability compared to intravenous administration. It is postulated that the movement of TQ-NLC through the intestinal lymphatic system bypasses the first metabolism and therefore enhances the relative bioavailability. However, oral administration has a slower absorption rate compared to intravenous administration where the AUC0-∞ was 4.539 times lower than the latter. CONCLUSION: TQ-NLC had better absorption when administered intravenously compared to oral administration. However, oral administration showed greater bioavailability compared to the intravenous route. This study provides the pharmacokinetics and biodistribution profile of TQ-NLC in vivo which is useful to assist researchers in clinical use.

A multifunctional nanomedicine platform for co-delivery of methotrexate and mild hyperthermia towards breast cancer therapy.

Methotrexate (MTX), an anti-neoplastic agent used for breast cancer treatment, has restricted clinical applications due to poor water solubility, non-specific targeting and adverse side effects. To overcome these limitations, MTX was co-encapsulated with an active-targeting platform known as superparamagnetic iron oxide nanoparticles (SPIONs) in a lipid-based homing system, nanostructured lipid carrier (NLC). This multi-modal therapeutic regime was successfully formulated with good colloidal stability, bio- and hemo-compatibility. MTX-SPIONs co-loaded NLC was time-dependent cytotoxic towards MDA-MB-231 breast cancer cell line with IC50 values of 137 µg/mL and 12 µg/mL at 48 and 72 h, respectively. The MTX-SPIONs co-loaded NLC was internalized in the MDA-MB-231 cells via caveolae-mediated endocytosis in a time-dependent manner, and the superparamagnetic properties were sufficient to induce, under a magnetic field, a localized temperature increase at cellular level resulting in apoptotic cell death. In conclusion, MTX-SPIONs co-loaded NLC is a potential magnetic guiding multi-modal therapeutic system for the treatment of breast cancer.

Migration and Proliferation Effects of Thymoquinone-Loaded Nanostructured Lipid Carrier (TQ-NLC) and Thymoquinone (TQ) on In Vitro Wound Healing Models.

Wound healing is a regulated biological event that involves several processes including infiltrating leukocyte subtypes and resident cells. Impaired wound healing is one of the major problems in diabetic patients due to the abnormal physiological changes of tissues and cells in major processes. Thymoquinone, a bioactive compound found in Nigella sativa has been demonstrated to possess antidiabetic, anti-inflammatory, and antioxidant effects. Today, the rapidly progressing nanotechnology sets a new alternative carrier to enhance and favour the speed of healing process. In order to overcome its low bioavailability, TQ is loaded into a colloidal drug carrier known as a nanostructured lipid carrier (NLC). This study aimed to determine the effect of TQ-NLC and TQ on cell proliferation and migration, mode of cell death, and the antioxidant levels in normal and diabetic cell models, 3T3 and 3T3-L1. Cytotoxicity of TQ-NLC and TQ was determined by MTT assay. The IC10 values obtained for 3T3-L1 treated with TQ-NLC and TQ for 24 hours were 4.7 ± 3.3 and 5.3 ± 0.6 µM, respectively. As for 3T3, the IC10 values obtained for TQ-NLC and TQ at 24 hours were 4.3 ± 0.17 and 3.9 ± 2.05 µM, respectively. TQ-NLC was observed to increase the number of 3T3 and 3T3-L1 healthy cells (87-95%) and gradually decrease early apoptotic cells in time- and dose-dependant manner compared with TQ. In the proliferation and migration assay, 3T3-L1 treated with TQ-NLC showed higher proliferation and migration rate (p < 0.05) compared with TQ. TQ-NLC also acted as an antioxidant by reducing the ROS levels in both cells after injury at concentration as low as 3 µM. Thus, this study demonstrated that TQ-NLC has better proliferation and migration as well as antioxidant effect compared with TQ especially on 3T3-L1 which confirms its ability as a good antidiabetic and antioxidant agent.

Cytotoxic Effect of Thymoquinone-Loaded Nanostructured Lipid Carrier (TQ-NLC) on Liver Cancer Cell Integrated with Hepatitis B Genome, Hep3B.

Thymoquinone (TQ), a bioactive compound found in Nigella sativa, cannot be orally consumed due to its lipophilicity. In order to overcome this low bioavailability, TQ is loaded into a colloidal drug carrier known as a nanostructured lipid carrier (NLC). This study aims to determine the antiproliferative effects of TQ and TQ-NLC on liver cancer cells integrated with the hepatitis B genome, Hep3B. The Hep3B was treated with TQ or TQ-NLC for 24, 48, and 72 hours via MTT assay. The results confirm that TQ or TQ-NLC inhibited the growth of Hep3B at IC50 <16.7 µM for 72 hours. TQ was also found to induce cell cycle arrest at the G1 checkpoint while TQ-NLC induced non-phase-specific cell cycle arrest. Further analysis using Annexin V staining confirmed the apoptotic induction of TQ or TQ-NLC via activation of caspases-3/7. In ROS management, TQ acted as a prooxidant (increased the level of ROS), while TQ-NLC acted as an antioxidant (reduced the level of ROS). Molecular analysis demonstrated that the GSH system and the Nrf2/Keap1 signaling pathway in Hep3B influenced the differential responses of the cells towards TQ or TQ-NLC. Hence, this study demonstrated that TQ and TQ-NLC have in vitro anticancer effects on the Hep3B.