The Analgesic Potential of Litsea Species: A Systematic Review.

Various plant species from the Litsea genus have been claimed to be beneficial for pain relief. The PRISMA approach was adopted to identify studies that reported analgesic properties of plants from the Litsea genus. Out of 450 records returned, 19 primary studies revealed the analgesic potential of nine Litsea species including (1) Litsea cubeba, (2) Litsea elliptibacea, (3) Litsea japonica, (4) Litsea glutinosa, (5) Litsea glaucescens, (6) Litsea guatemalensis, (7) Litsea lancifolia, (8) Litsea liyuyingi and (9) Litsea monopetala. Six of the species, 1, 3, 4, 7, 8 and 9, demonstrated peripheral antinociceptive properties as they inhibited acetic-acid-induced writhing in animal models. Species 1, 3, 4, 8 and 9 further showed effects via the central analgesic route at the spinal level by increasing the latencies of heat stimulated-nocifensive responses in the tail flick assay. The hot plate assay also revealed the efficacies of 4 and 9 at the supraspinal level. Species 6 was reported to ameliorate hyperalgesia induced via partial sciatic nerve ligation (PSNL). The antinociceptive effects of 1 and 3 were attributed to the regulatory effects of their bioactive compounds on inflammatory mediators. As for 2 and 5, their analgesic effect may be a result of their activity with the 5-hydroxytryptamine 1A receptor (5-HT1AR) which disrupted the pain-stimulating actions of 5-HT. Antinociceptive activities were documented for various major compounds of the Litsea plants. Overall, the findings suggested Litsea species as good sources of antinociceptive compounds that can be further developed to complement or substitute prescription drugs for pain management.

Hematological, biochemical, and histopathological evaluation of the Morus alba L. leaf extract from Brunei Darussalam: Acute toxicity study in ICR mice.

Background: Studies have reported that the phytochemical content of Mulberry (Morus alba Linn.) is influenced by the area where it grows. On the other hand, the study of the bioactivity and toxicity of mulberry leaves from Brunei Darussalam still needs to be completed. In particular, the investigation regarding the safe dose for Mulberry's application from Brunei Darussalam has yet to be studied. Hence, toxicity information must be considered even though the community has used it for generations. Aim: This study investigated Morus alba ethanolic leaf extract (MAE) to observe the acute toxicity in mice. Methods: In particular, this study utilized 12 female Institute of Cancer Research mice, 8 weeks old, divided into 2 groups: the control group and the MAE group (2,000 mg/kg single dose). Physiology, hematology, biochemistry, and histology were analyzed during the study. Results: The examination result indicated no mortality and behavioral changes throughout the testing period. However, the mice developed mild anemia and leukopenia, followed by decreased numbers of neutrophils, lymphocytes, and monocytes. In addition, the mice developed a mild hepatocellular injury, indicated by significant (p < 0.05) elevations of both alanine aminotransferase (ALT) and aspartate transaminase (AST). The histopathological findings of the liver were also consistent with the increment of ALT and AST, indicating mild hepatocellular necrosis through the eosinophilic cytoplasm and pyknosis (p > 0.05). Conclusion: It was evident that a single oral administration of MAE was not lethal for mice (LD50, which was higher than 2,000 mg/kg). However, the administration of high doses of MAE must be carefully considered.

Bioactivity, phytochemistry studies and subacute in vivo toxicity of ethanolic leaf extract of white mulberry (Morus alba linn.) in female mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional uses of Morus alba L. leaf extracts (MLE) have been reported for treating hyperglycaemia and diabetes. Phytochemical compounds in the leaves demonstrated the ability to enhance insulin sensitivity and ß-cell secretory function, suggesting their potential value in reducing blood glucose and treating diabetes. However, the phytochemical constituents and safety of the herbal medicines need to be verified in each experimental field from different growing areas. Studies on the phytochemistry and toxicity of Morus alba leaves in Southeast Asia, especially in Brunei, have never been investigated. AIM OF THE STUDY: This study aimed to investigate the bioactivity and phytochemistry of Morus alba ethanolic leaf extract from Brunei Darussalam and its subacute toxic effects in the Institute of Cancer Research (ICR) female mice. MATERIALS AND METHODS: The phenolic yield and antioxidant of the extract were analysed. Meanwhile, liquid chromatography-mass spectrometry and high-performance liquid chromatography were utilised to determine the phenolic compound of the MLE. In the subacute toxicity study, twenty-five female mice were randomly divided into five groups: the control group, which received oral gavage of 5% dimethyl sulfoxide solvent (DMSO), and the MLE treatment group, which received the extract at a dose of 125, 250, 500 and 1000 mg/kg. Physiology, haematology, biochemistry, and histology were evaluated during the study. RESULTS: Morus alba leaf depicted total phenolic 10.93 mg gallic acid equivalents (GAE)/g dry weight (DW), flavonoid 256.67 mg quercetin equivalents (QE)/g DW, and antioxidant bioactivity content of 602.03 IC50 µg/mL and 13.21 mg Fe2+/g DW. Twenty compounds in the Morus alba ethanolic leaf extract were identified, with chlorogenic acid (305.60 mg/100 g DW) as the primary compound. As for subacute toxicity in this study, neither mortality nor haematological changes were observed. On the other hand, administration of 500 and 1000 mg/kg MLE resulted in mild hepatocellular injury, as indicated by a significant (p < 0.05) increase in liver enzyme activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The histopathological score showed mild hepatocellular necrosis in administering 250, 500, and 1000 mg/kg of MLE. The parameters of renal injury were within normal limits, with the increase in eosinophilic cytoplasm observed in the histological scoring at 1000 mg/kg of MLE. CONCLUSIONS: Morus alba leaf extract showed abundant polyphenols. In a study on subacute toxicity, MLE caused mild hepatotoxicity in mice. The toxic effect of the extract may be due to kaempferol and chlorogenic acid compounds. The 125 mg/kg MLE dose was safe with no adverse effects.

Identification and optimization of TDP1 inhibitors from anthraquinone and chalcone derivatives: consensus scoring virtual screening and molecular simulations.

Virtual screening aims to identify and rank compounds with drug/lead-like properties based on their affinity for the protein target. We developed a methodology that integrates structure- and ligand-based screening approaches to enhance hit rates against the TDP1 protein within a database of anthraquinone and chalcone derivatives, followed by evaluation of prioritized compounds through molecular simulations. This technique is particularly useful for training set imbalances. Four screening methods were used: QSAR, pharmacophore, shape similarity, and docking. Each method was individually trained to score compounds, and the scores were fused to create parallel Z-score fusion. The QSAR models exhibited satisfactory R2 values (0.84 to 0.75), whereas the pharmacophoric and shape similarity models demonstrated excellent performance (ROC:0.82-0.88). Docking enrichment analysis identified 6N0D as the optimal TDP1 crystal structure (ROC = 0.73). Remarkably, the consensus scoring method surpassed other screening methods, achieving the highest ROC value of 0.98. Docking screening prioritized compounds with binding modes resembling the co-crystallized ligands, whereas MMGBSA, consensus, and docking produced dynamic simulations that were as stable as the co-crystallized ligands. Additionally, the QSAR-selected compounds exhibited binding modes similar to those of commercially available TDP1 inhibitors. In this study, a strong correlation was found between the inhibitory concentrations and binding energy values of commercialized TDP1 inhibitors, indicating that the top-ranked compounds are expected to have potent inhibitory effects in the nano-/micromolar range. The results of this study establish that consensus scoring can be used as an adaptable mainstay virtual screening methodology, pending subsequent experimental validation for affirmation.Communicated by Ramaswamy H. Sarma.

Insights into the computer-aided drug design and discovery based on anthraquinone scaffold for cancer treatment: A protocol for systematic review.

There is still unmet medical need in cancer treatment mainly due to drug resistance and adverse drug events. Therefore, the search for better drugs is essential. Computer-aided drug design (CADD) and discovery tools are useful to streamline the lengthy and costly drug development process. Anthraquinones are a group of naturally occurring compounds with unique scaffold that exert various biological properties including anticancer activities. This protocol describes a systematic review that provide insights into the computer-aided drug design and discovery based on anthraquinone scaffold for cancer treatment. It was prepared in accordance with the "Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 guidelines, and published in the "International prospective register of systematic reviews" database (PROSPERO: CRD42023432904). Search strategies will be developed based on the combination of relevant keywords and executed in PubMed, Scopus, Web of Science and MedRxiv. Only original studies that employed CADD as primary tool in virtual screening for the purpose of designing or discovering anti-cancer drugs involving anthraquinone scaffold published in English language will be included. Two independent reviewers will be involved to screen and select the papers, extract the data and assess the risk of bias. Apart from exploring the trends and types of CADD methods used, the target proteins of these compounds in cancer treatment will also be revealed in this review. It is believed that the outcome of this study could be utilized to support the ongoing research in similar area with better quality and greater probability of success, consequently optimizing the resources in subsequent in vitro, in vivo, non-clinical and clinical development. It will also serve as an evidence based scientific guide for new research to design novel anthraquinone-derived drug with improved efficacy and safety profile for cancer treatment.

Natural products as novel anti-obesity agents: insights into mechanisms of action and potential for therapeutic management.

Obesity affects more than 10% of the adult population globally. Despite the introduction of diverse medications aimed at combating fat accumulation and obesity, a significant number of these pharmaceutical interventions are linked to substantial occurrences of severe adverse events, occasionally leading to their withdrawal from the market. Natural products serve as attractive sources for anti-obesity agents as many of them can alter the host metabolic processes and maintain glucose homeostasis via metabolic and thermogenic stimulation, appetite regulation, pancreatic lipase and amylase inhibition, insulin sensitivity enhancing, adipogenesis inhibition and adipocyte apoptosis induction. In this review, we shed light on the biological processes that control energy balance and thermogenesis as well as metabolic pathways in white adipose tissue browning, we also highlight the anti-obesity potential of natural products with their mechanism of action. Based on previous findings, the crucial proteins and molecular pathways involved in adipose tissue browning and lipolysis induction are uncoupling protein-1, PR domain containing 16, and peroxisome proliferator-activated receptor-γ in addition to Sirtuin-1 and AMP-activated protein kinase pathway. Given that some phytochemicals can also lower proinflammatory substances like TNF-α, IL-6, and IL-1 secreted from adipose tissue and change the production of adipokines like leptin and adiponectin, which are important regulators of body weight, natural products represent a treasure trove for anti-obesity agents. In conclusion, conducting comprehensive research on natural products holds the potential to accelerate the development of an improved obesity management strategy characterized by heightened efficacy and reduced incidence of side effects.

Prevention and Treatment of Monkeypox: A Systematic Review of Preclinical Studies.

The outbreak of monkeypox, coupled with the onslaught of the COVID-19 pandemic is a critical communicable disease. This study aimed to systematically identify and review research done on preclinical studies focusing on the potential monkeypox treatment and immunization. The presented juxtaposition of efficacy of potential treatments and vaccination that had been tested in preclinical trials could serve as a useful primer of monkeypox virus. The literature identified using key terms such as monkeypox virus or management or vaccine stringed using Boolean operators was systematically reviewed. Pubmed, SCOPUS, Cochrane, and preprint databases were used, and screening was performed in accordance with PRISMA guidelines. A total of 467 results from registered databases and 116 from grey literature databases were screened. Of these results, 72 studies from registered databases and three grey literature studies underwent full-text screening for eligibility. In this systematic review, a total of 27 articles were eligible according to the inclusion criteria and were used. Tecovirimat, known as TPOXX or ST-246, is an antiviral drug indicated for smallpox infection whereas brincidofovir inhibits the viral DNA polymerase after incorporation into viral DNA. The ability of tecovirimat in providing protection to poxvirus-challenged animals from death had been demonstrated in a number of animal studies. Non-inferior with regard to immunogenicity was reported for the live smallpox/monkeypox vaccine compared with a single dose of a licensed live smallpox vaccine. The trial involving the live vaccine showed a geometric mean titre of vaccinia-neutralizing antibodies post two weeks of the second dose of the live smallpox/monkeypox vaccine. Of note, up to the third generation of smallpox vaccines-particularly JYNNEOS and Lc16m8-have been developed as preventive measures for MPXV infection and these vaccines had been demonstrated to have improved safety compared to the earlier generations.

Pharmacotherapeutics Applications and Chemistry of Chalcone Derivatives.

Chalcones have been well examined in the extant literature and demonstrated antibacterial, antifungal, anti-inflammatory, and anticancer properties. A detailed evaluation of the purported health benefits of chalcone and its derivatives, including molecular mechanisms of pharmacological activities, can be further explored. Therefore, this review aimed to describe the main characteristics of chalcone and its derivatives, including their method synthesis and pharmacotherapeutics applications with molecular mechanisms. The presence of the reactive α,ß-unsaturated system in the chalcone's rings showed different potential pharmacological properties, including inhibitory activity on enzymes, anticancer, anti-inflammatory, antibacterial, antifungal, antimalarial, antiprotozoal, and anti-filarial activity. Changing the structure by adding substituent groups to the aromatic ring can increase potency, reduce toxicity, and broaden pharmacological action. This report also summarized the potential health benefits of chalcone derivatives, particularly antimicrobial activity. We found that several chalcone compounds can inhibit diverse targets of antibiotic-resistance development pathways; therefore, they overcome resistance, and bacteria become susceptible to antibacterial compounds. A few chalcone compounds were more active than conventional antibiotics, like vancomycin and tetracycline. On another note, a series of pyran-fused chalcones and trichalcones can block the NF-B signaling complement system implicated in inflammation, and several compounds demonstrated more potent lipoxygenase inhibition than NSAIDs, such as indomethacin. This report integrated discussion from the domains of medicinal chemistry, organic synthesis, and diverse pharmacological applications, particularly for the development of new anti-infective agents that could be a useful reference for pharmaceutical scientists.

Comparative analysis of an anthraquinone and chalcone derivatives-based virtual combinatorial library. A cheminformatics "proof-of-concept" study.

A Laplacian scoring algorithm for gene selection and the Gini coefficient to identify the genes whose expression varied least across a large set of samples were the state-of-the-art methods used here. These methods have not been trialed for their feasibility in cheminformatics. This was a maiden attempt to investigate a complete comparative analysis of an anthraquinone and chalcone derivatives-based virtual combinatorial library. This computational "proof-of-concept" study illustrated the combinatorial approach used to explain how the structure of the selected natural products (NPs) undergoes molecular diversity analysis. A virtual combinatorial library (1.6 M) based on 20 anthraquinones and 24 chalcones was enumerated. The resulting compounds were optimized to the near drug-likeness properties, and the physicochemical descriptors were calculated for all datasets including FDA, Non-FDA, and NPs from ZINC 15. UMAP and PCA were applied to compare and represent the chemical space coverage of each dataset. Subsequently, the Laplacian score and Gini coefficient were applied to delineate feature selection and selectivity among properties, respectively. Finally, we demonstrated the diversity between the datasets by employing Murcko's and the central scaffolds systems, calculating three fingerprint descriptors and analyzing their diversity by PCA and SOM. The optimized enumeration resulted in 1,610,268 compounds with NP-Likeness, and synthetic feasibility mean scores close to FDA, Non-FDA, and NPs datasets. The overlap between the chemical space of the 1.6 M database was more prominent than with the NPs dataset. A Laplacian score prioritized NP-likeness and hydrogen bond acceptor properties (1.0 and 0.923), respectively, while the Gini coefficient showed that all properties have selective effects on datasets (0.81-0.93). Scaffold and fingerprint diversity indicated that the descending order for the tested datasets was FDA, Non-FDA, NPs and 1.6 M. Virtual combinatorial libraries based on NPs can be considered as a source of the combinatorial compound with NP-likeness properties. Furthermore, measuring molecular diversity is supposed to be performed by different methods to allow for comparison and better judgment.

Target-Based Small Molecule Drug Discovery for Colorectal Cancer: A Review of Molecular Pathways and In Silico Studies.

Colorectal cancer is one of the most prevalent cancer types. Although there have been breakthroughs in its treatments, a better understanding of the molecular mechanisms and genetic involvement in colorectal cancer will have a substantial role in producing novel and targeted treatments with better safety profiles. In this review, the main molecular pathways and driver genes that are responsible for initiating and propagating the cascade of signaling molecules reaching carcinoma and the aggressive metastatic stages of colorectal cancer were presented. Protein kinases involved in colorectal cancer, as much as other cancers, have seen much focus and committed efforts due to their crucial role in subsidizing, inhibiting, or changing the disease course. Moreover, notable improvements in colorectal cancer treatments with in silico studies and the enhanced selectivity on specific macromolecular targets were discussed. Besides, the selective multi-target agents have been made easier by employing in silico methods in molecular de novo synthesis or target identification and drug repurposing.

Synergy between machine learning and natural products cheminformatics: Application to the lead discovery of anthraquinone derivatives.

Cheminformatics utilizing machine learning (ML) techniques have opened up a new horizon in drug discovery. This is owing to vast chemical space expansion with rocketing numbers of expected hits and lead compounds that match druggable macromolecular targets, in particular from natural compounds. Due to the natural products' (NP) structural complexity, uniqueness, and diversity, they could occupy a bigger space in pharmaceuticals, allowing the industry to pursue more selective leads in the nanomolar range of binding affinity. ML is an essential part of each step of the drug design pipeline, such as target prediction, compound library preparation, and lead optimization. Notably, molecular mechanic and dynamic simulations, induced docking, and free energy perturbations are essential in predicting best binding poses, binding free energy values, and molecular mechanics force fields. Those applications have leveraged from artificial intelligence (AI), which decreases the computational costs required for such costly simulations. This review aimed to describe chemical space and compound libraries related to NPs. High-throughput screening utilized for fractionating NPs and high-throughput virtual screening and their strategies, and significance, are reviewed. Particular emphasis was given to AI approaches, ML tools, algorithms, and techniques, especially in drug discovery of macrocyclic compounds and approaches in computer-aided and ML-based drug discovery. Anthraquinone derivatives were discussed as a source of new lead compounds that can be developed using ML tools for diverse medicinal uses such as cancer, infectious diseases, and metabolic disorders. Furthermore, the power of principal component analysis in understanding relevant protein conformations, and molecular modeling of protein-ligand interaction were also presented. Apart from being a concise reference for cheminformatics, this review is a useful text to understand the application of ML-based algorithms to molecular dynamics simulation and in silico absorption, distribution, metabolism, excretion, and toxicity prediction.

General Health Benefits and Pharmacological Activities of Triticum aestivum L.

Common wheat (Triticum aestivum), one of the world's most consumed cereal grains, is known for its uses in baking and cooking in addition to its medicinal uses. As this plant's medical benefits are enormous and scattered, this narrative review was aimed at describing the pharmacological activities, phytochemistry, and the nutritional values of Triticum aestivum. It is a good source of dietary fiber, resistant starch, phenolic acids, alkylresorcinols, lignans, and diverse antioxidant compounds such as carotenoids, tocopherols and tocotrienols. These constituents provide Triticum aestivum with a wide range of pharmacological properties, including anticancer, antimicrobial, antidiabetic, hypolipemic, antioxidant, laxative, and moisturizing effects. This review summarized the established benefits of wheat in human health, the mode of action, and different clinical, in vitro and in vivo studies for different varieties and cultivars. This review also gives an insight for future research into the better use of this plant as a functional food. More clinical trials, in vivo and in vitro studies are warranted to broaden the knowledge about the effect of Triticum aestivum on nutrition-related diseases prevention, and physical and mental well-being sustenance.

Cancer protective effects of plums: A systematic review.

Plums is one of the most cultivated stone fruits due to its fast growing popularity. It has various traditionally recognized health benefits. There are two main commercial types of plums: the European plum (Prunus domestica) and the Japanese plum (Prunus salicina), each having many varieties. Researchers are gathering further evidence of pharmacological effects for plums by scientifically studying its anti-inflammatory, antioxidant properties. A systematic review analysing the literature related to the effects of plums on prevention and treatment of cancer is warranted. This is the first review examining the cancer-related effects of plums. Antioxidation properties of the active constituents of plum were also compared. Scopus, Google Scholar, PubMed, Medxriv and Cochrane Library databases, from their date of inception until July 2021 were utilized. The risk of bias was assessed using CONSORT checklist. A total of 6639 studies were screened and eventually only 54 studies were included. Full-text review of included studies revealed that plum extracts were rich in antioxidants. Overall, most of the studies that fulfilled the eligibility criteria were in vitro and a few clinical studies involving in vivo work. Therefore, it would be beneficial to perform more studies on animals or humans, to confirm that the result obtained from these in vitro studies are able to be extrapolated in a wider range of applications. Further clinical and in vivo studies are warranted to validate plums as a functional food for treatment and prevention of cancer.

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.

Phytochemical and Therapeutic Potential of Citrus grandis (L.) Osbeck: A Review.

Citrus grandis or Citrus maxima, widely recognized as Pomelo is widely cultivated in many countries because of their large amounts of functional, nutraceutical and biological activities. In traditional medicine, various parts of this plant including leaf, pulp and peel are used for generations as they are scientifically proven to have therapeutic potentials and safe for human use. The main objective of this study was to review the different therapeutic applications of Citrus grandis and the phytochemicals associated with its medicinal values. In this article different pharmacological properties like antimicrobial, antitumor, antioxidant, anti-inflammatory, anticancer, antiepileptic, stomach tonic, cardiac stimulant, cytotoxic, hepatoprotective, nephroprotective, and anti-diabetic activities of the plant are highlighted. The enrichment of the fruit with flavonoids, polyphenols, coumarins, limonoids, acridone alkaloids, essential oils and vitamins mainly helps in exhibiting the pharmacological activities within the body. The vitamins enriched fruit is rich in nutritional value and also has minerals like calcium, phosphorous, sodium and potassium, which helps in maintaining the proper health and growth of the bones as well as the electrolyte balance of the body. To conclude, various potential therapeutic effects of Citrus grandis have been demonstrated in recent literature. Further studies on various parts of fruit, including pulp, peel, leaf, seed and it essential oil could unveil additional pharmacological activities which can be beneficial to the mankind.

Herbal Plants: The Role of AhR in Mediating Immunomodulation.

The prevalence of chronic inflammatory diseases including inflammatory bowel disease (IBD), autoimmunity and cancer have increased in recent years. Herbal-based compounds such as flavonoids have been demonstrated to contribute to the modulation of these diseases although understanding their mechanism of action remains limited. Flavonoids are able to interact with cellular immune components in a distinct way and influence immune responses at a molecular level. In this mini review, we highlight recent progress in our understanding of the modulation of immune responses by the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor whose activity can be regulated by diverse molecules including flavonoids. We focus on the role of AhR in integrating signals from flavonoids to modulate inflammatory responses using in vitro and experimental animal models. We also summarize the limitations of these studies. Medicinal herbs have been widely used to treat inflammatory disorders and may offer a valuable therapeutic strategy to treat aberrant inflammatory responses by modulation of the AhR pathway.

Overcoming Chemoresistance via Extracellular Vesicle Inhibition.

With the ever-growing number of cancer deaths worldwide, researchers have been working hard to identify the key reasons behind the failure of cancer therapies so the efficacy of those therapies may be improved. Based on extensive research activities and observations done by researchers, chemoresistance has been identified as a major contributor to the drastic number of deaths among cancer patients. Several factors have been linked to formation of chemoresistance, such as chemotherapy drug efflux, immunosuppression, and epithelial-mesenchymal transition (EMT). Lately, increasing evidence has shed light on the role of extracellular vesicles (EVs) in the regulation of chemoresistance. However, there is limited research into the possibility that inhibiting EV release or uptake in cancer cells may curb chemoresistance, allowing chemotherapy drugs to target cancer cells without restriction. Prominent inhibitors of EV uptake and release in cancer cells have been compiled and contrasted in this review. This is in the hope of sparking greater interest in the field of EV-mediated chemoresistance, as well as to provide an overview of the field for fundamental and clinical research communities, particularly in the field of cancer resistance research. In-depth studies of EV-mediated chemoresistance and EV inhibitors in cancer cells would spur significant improvement in cancer treatments which are currently available.

Knowledge Attitude and Practice of traditional and complementary / alternative medicines amongst End Stage Renal Disease patients in Brunei Darussalam.

OBJECTIVE: A limited study was found in regards to knowledge, attitudes, and practices (KAP) of traditional and complementary/alternative medicines (TCAM) amongst end-stage renal disease (ESRD) in South East Asian region including Brunei Darussalam. This study explored TCAM use amongst ESRD patients in Brunei Darussalam. METHODS: This was a cross-sectional study in a local Dialysis Centre using a bilingual self-structured questionnaire. Recruitment was done using systematic random sampling with certain inclusion criteria. All collected data were entered into Microsoft Excel 2016, and inferential statistics were carried out using R studio version 1.1.383. RESULTS: About 40.2% were TCAM users, and this was not predictable by any sociodemographic background. Nevertheless, compliance with conventional medicine (CM) was very high (94.1%). Users had a more positive disease perception, which was not affected by length on dialysis treatment or the presence of comorbidities. TCAM was perceived to be less effective and unsafe compared to CM, and patients agreed that its use should be monitored and notified. Health supplement (70.7%) was mainly used to improve general wellness (48.5%) or to relieve fatigue (42.4%), and most practices were influenced by family (43.9%). Only a minority of users (19.5%) reported side effects as majority (80.5%) consumed TCAM and CM separately. CONCLUSIONS: High TCAM practice showed that there are still needs that are not fulfilled. The health care professionals should always remain vigilant of its use and be attentive to attend to patients' needs.

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.

Coriandrum sativum L.: A Review on Ethnopharmacology, Phytochemistry, and Cardiovascular Benefits.

Coriandrum sativum (C. sativum), belonging to the Apiaceae (Umbelliferae) family, is widely recognized for its uses in culinary and traditional medicine. C. sativum contains various phytochemicals such as polyphenols, vitamins, and many phytosterols, which account for its properties including anticancer, anti-inflammatory, antidiabetic, and analgesic effects. The cardiovascular benefits of C. sativum have not been summarized before, hence this review aims to further evaluate and discuss its effectiveness in cardiovascular diseases, according to the recent literature. An electronic search for literature was carried out using the following databases: PubMed, Scopus, Google Scholar, preprint platforms, and the Cochrane Database of Systematic Reviews. Articles were gathered from the inception of the database until August 2021. Moreover, the traditional uses and phytochemistry of coriander were surveyed in the original resources and summarized. As a result, most of the studies that cover cardiovascular benefits and fulfilled the eligibility criteria were in vivo, while only a few were in vitro and clinical studies. In conclusion, C. sativum can be deemed a functional food due to its wide range of cardiovascular benefits such as antihypertensive, anti-atherogenic, antiarrhythmic, hypolipidemic as well as cardioprotective effects.