Ethnobotany, Phytochemistry, and Biological Activities of the Genus Cordyline.

Cordyline species have a long history in traditional medicine as a basis of treatment for various ailments such as a bloody cough, dysentery, and a high fever. There are about 26 accepted species names in this genus distributed worldwide, including C. fruticosa, C. autralis, C. stricta, C. cannifolia, and C. dracaenosides. This work presents a comprehensive review of the traditional uses of plants of the genus Cordylie and their chemical constituents and biological activities. A bibliographic search was conducted to identify available information on ethnobotany, ethnopharmacology, chemical composition, and biological activities. A total of 98 isolated compounds potentially responsible for most of the traditional medicinal applications have been reported from eight species of Cordyline and are characterised as flavonoid, spirostane, furostane, and cholestane glycosides. Some of these pure compounds, as well as extracts from some species of Cordyline, have exhibited noteworthy anti-oxidant, antiproliferative, antimicrobial, and hypolipidemic activities. Although many of these species have not yet been investigated phytochemically or pharmacologically, they remain a potential source of new bioactive compounds.

Vitamin D supplementation in a post-pandemic era: A narrative review.

Vitamin D is a fat-soluble molecule referring to the different isoforms, ergocalciferol (D2) and cholecalciferol (D3). Its physiological functions include increasing calcium serum concentrations. 25-hydroxyvitamin D3 (25(OH)D) (Calcifediol), a non-active, circulating instant precursor is seen as a pre-hormone. Studies have shown that a deficiency in calcifediol is related to chronic conditions such as cardiovascular, musculoskeletal, immune system, neurological, and anti-neoplastic functions. Vitamin D supplementation has shown its benefit as prophylaxis and treatment during the coronavirus disease 2019 (COVID-19) pandemic and an increase in the prescribing of vitamin D supplementation has been observed. The intention of this review article is to provide guidance on the recommended dosage regimen as a prophylactic measure during COVID-19 and its use as a supplement in general. From this review article, it is clear that vitamin D has an important role to play not only in COVID-19 but also in various other health aspects of the human body.Contribution: This review article highlighted the role of vitamin D in managing vitamin D deficiency and its role as a supplement in the management of respiratory tract infections, especially COVID-19. This overview can assist physicians in optimising healthcare by optimised dosing recommendations and indications.

Sugars and Polyols of Natural Origin as Carriers for Solubility and Dissolution Enhancement.

Crystalline carriers such as dextrose, sucrose, galactose, mannitol, sorbitol, and isomalt have been reported to increase the solubility, and dissolution rates of poorly soluble drugs when employed as carriers in solid dispersions (SDs). However, synthetic polymers dominate the preparation of drugs: excipient SDs have been created in recent years, but these polymer-based SDs exhibit the major drawback of recrystallisation upon storage. Also, the use of high-molecular-weight polymers with increased chain lengths brings forth problems such as increased viscosity and unnecessary bulkiness in the resulting dosage form. An ideal SD carrier should be hydrophilic, non-hygroscopic, have high hydrogen-bonding propensity, have a high glass transition temperature (Tg), and be safe to use. This review discusses sugars and polyols as suitable carriers for SDs, as they possess several ideal characteristics. Recently, the use of low-molecular-weight excipients has gained much interest in developing SDs. However, there are limited options available for safe, low molecular excipients, which opens the door again for sugars and polyols. The major points of this review focus on the successes and failures of employing sugars and polyols in the preparation of SDs in the past, recent advances, and potential future applications for the solubility enhancement of poorly water-soluble drugs.

Antiplasmodial and Antileishmanial Activities of a New Limonoid and Other Constituents from the Stem Bark of Khaya senegalensis.

Plasmodium falciparum and Leishmania sp. resistance to antiparasitic drugs has become a major concern in malaria and leishmaniasis control. These diseases are public health problems with significant socioeconomic impacts, and mostly affect disadvantaged populations living in remote tropical areas. This challenge emphasizes the need to search for new chemical scaffolds that preferably possess novel modes of action to contribute to antimalarial and antileishmanial research programs. This study aimed to investigate the antimalarial and antileishmanial properties of a methanol extract (KS-MeOH) of the stem bark of the Cameroonian medicinal plant Khaya senegalensis and its isolated compounds. The purification of KS-MeOH led to the isolation of a new ordered limonoid derivative, 21ß-hydroxybourjotinolone A (1a), together with 15 known compounds (1bc-14) using a repeated column chromatography. Compound 1a was obtained in an epimeric mixture of 21α-melianodiol (1b) and 21ß-melianodiol (1c). Structural characterization of the isolated compounds was achieved with HRMS, and 1D- and 2D-NMR analyses. The extracts and compounds were screened using pre-established in vitro methods against synchronized ring stage cultures of the multidrug-resistant Dd2 and chloroquine-sensitive/sulfadoxine-resistant 3D7 strains of Plasmodium falciparum and the promastigote form of Leishmania donovani (1S(MHOM/SD/62/1S). In addition, the samples were tested for cytotoxicity against RAW 264.7 macrophages. Positive controls consisted of artemisinin and chloroquine for P. falciparum, amphotericin B for L. donovani, and podophyllotoxin for cytotoxicity against RAW 264.7 cells. The extract and fractions exhibited moderate to potent antileishmanial activity with 50% inhibitory concentrations (IC50) ranging from 5.99 ± 0.77 to 2.68 ± 0.42 µg/mL, while compounds displayed IC50 values ranging from 81.73 ± 0.12 to 6.43 ± 0.06 µg/mL. They were weakly active against the chloroquine-sensitive/sulfadoxine-resistant Pf3D7 strain but highly potent toward the multidrug-resistant PfDd2 (extracts, IC50 2.50 ± 0.12 to 4.78 ± 0.36 µg/mL; compounds IC50 2.93 ± 0.02 to 50.97 ± 0.37 µg/mL) with selectivity indices greater than 10 (SIDd2 > 10) for the extract and fractions and most of the derived compounds. Of note, the limonoid mixture [21ß-hydroxylbourjotinolone A (1a) + 21α-melianodiol (1b) + 21ß-melianodiol (1c)] exhibited moderate activity against P. falciparum and L. donovani. This novel antiplasmodial and antileishmanial chemical scaffold qualifies as a promising starting point for further medicinal chemistry-driven development of a dually active agent against two major infectious diseases affecting humans in Africa.

Exploring novel strategies to improve anti-tumour efficiency: The potential for targeting reactive oxygen species.

The cellular milieu in which malignant growths or cancer stem cells reside is known as the tumour microenvironment (TME). It is the consequence of the interactivity amongst malignant and non-malignant cells and directly affects cancer development and progression. Reactive oxygen species (ROS) are chemically reactive molecules that contain oxygen, they are generated because of numerous endogenous and external factors. Endogenous ROS produced from mitochondria is known to significantly increase intracellular oxidative stress. In addition to playing a key role in several biological processes both in healthy and malignant cells, ROS function as secondary messengers in cell signalling. At low to moderate concentrations, ROS serves as signalling transducers to promote cancer cell motility, invasion, angiogenesis, and treatment resistance. At high concentrations, ROS can induce oxidative stress, leading to DNA damage, lipid peroxidation and protein oxidation. These effects can result in cell death or trigger signalling pathways that lead to apoptosis. The creation of innovative therapies and cancer management techniques has been aided by a thorough understanding of the TME. At present, surgery, chemotherapy, and radiotherapy, occasionally in combination, are the most often used methods for tumour treatment. The current challenge that these therapies face is the lack of spatiotemporal application specifically at the lesion which results in toxic effects on healthy cells associated with off-target drug delivery and undesirably high doses. Nanotechnology can be used to specifically deliver various chemicals via nanocarriers to target tumour cells, thereby increasing the accumulation of ROS-inducing agents at the site of the tumour. Nanoparticles can be engineered to release ROS-inducing agents in a controlled manner to the TME that will in turn react with the ROS to either increase or decrease it, thereby improving antitumour efficiency. Nano-delivery systems such as liposomes, nanocapsules, solid lipid nanoparticles and nanostructured lipid carriers were explored for the up/down-regulation of ROS. This review will discuss the use of nanotechnology in targeting and altering the ROS in the TME.

Antileishmanial and Antiplasmodial Activities of Secondary Metabolites from the Root of Antrocaryon klaineanum Pierre (Anacardiaceae).

Antrocaryon klaineanum is traditionally used for the treatment of back pain, malaria, female sterility, chlamydiae infections, liver diseases, wounds, and hemorrhoid. This work aimed at investigating the bioactive compounds with antileishmanial and antiplasmodial activities from A. klaineanum. An unreported glucocerebroside antroklaicerebroside (1) together with five known compounds (2-6) were isolated from the root barks of Antrocaryon klaineanum using chromatographic techniques. The NMR, MS, and IR spectroscopic data in association with previous literature were used for the characterization of all the isolated compounds. Compounds 1-4 are reported for the first time from A. klaineanum. The methanol crude extract (AK-MeOH), the n-hexane fraction (AK-Hex), the dichloromethane fraction (AK-DCM), the ethyl acetate fraction (AK-EtOAc), and compounds 1-6 were all evaluated for their antiparasitic effects against Plasmodium falciparum strains susceptible to chloroquine (3D7), resistant to chloroquine (Dd2), and promastigotes of Leishmania donovani (MHOM/SD/62/1S). The AK-Hex, AK-EtOAc, AK-MeOH, and compound 2 were strongly active against Dd2 strain with IC50 ranging from 2.78 ± 0.06 to 9.30 ± 0.29 µg/mL. Particularly, AK-MeOH was the most active-more than the reference drugs used-with an IC50 of 2.78 ± 0.06 µg/mL. The AK-EtOAc as well as all the tested compounds showed strong antileishmanial activities with IC50 ranging from 4.80 ± 0.13 to 9.14 ± 0.96 µg/mL.

Iridoid Derivatives as Anticancer Agents: An Updated Review from 1970-2022.

The rise of cancer cases has coincided with the urgent need for the development of potent chemical entities and/or modification of existing commodities to improve their efficacy. Increasing evidence suggests that cancer remains one of the leading causes of death globally, with colon cancer cases alone likely to rise exponentially by 2030. The exponential rise in cancer prevalence is largely attributable to the growing change toward a sedentary lifestyle and modern diets, which include genetically modified foods. At present, the prominent treatments for cancer are chemotherapy, surgery, and radiation. Despite slowing cancer progression, these treatments are known to have devastating side effects that may deteriorate the health of the patient, thus, have a low risk-benefit ratio. In addition, many cancer drugs have low bioavailability, thereby limiting their therapeutic effects in cancer patients. Moreover, the drastic rise in the resistance of neoplastic cells to chemotherapeutic agents is rendering the use of some drugs ineffective, thereby signaling the need for more anticancer chemical entities. As a result, the use of natural derivatives as anticancer agents is gaining considerable attention. Iridoids have the potential to form conjugates with other anticancer, antidiabetic, antileishmanial, and antimalarial drugs, which synergistically have the potential to increase their effects. Published studies have identified the role of iridoids, which, if fully explored, may result in cheaper and less toxic alternative/adjuvant cancer drugs. The subject of this article is natural and synthetic iridoid derivatives and their potential therapeutic roles as anticancer agents.

Antiretroviral stewardship in a tertiary academic hospital: The need for a clinical pharmacist.

Background: South Africa has the highest prevalence of people living with HIV globally. Although antiretroviral therapy provides solutions, evidence of antiretroviral resistance emerged, requiring the application of antiretroviral-stewardship programmes to curb medication-related problems. Aim: Identify and describe antiretroviral-stewardship pharmacist interventions in an active antiretroviral-stewardship programme. Setting: HIV-positive adults admitted to medical wards at a tertiary academic hospital in South Africa. Methods: A descriptive quantitative study was performed, utilising an antiretroviral-stewardship assessment tool to determine antiretroviral-related recommendations in the treatment of HIV-positive adults. The study employed purposive sampling. Treatment charts were evaluated to identify antiretroviral-stewardship recommendations. The number of recommendations highlighted the need for a clinical pharmacist in an active antiretroviral-stewardship programme. Descriptive data analysis with Pearson correlations was employed to display the data. Results: Medication-related problems were identified in 100% of study patients (n = 41), with an average of 2.46 interventions per patient. One-hundred-and-one medication-related problems were identified by using the antiretroviral-stewardship assessment tool. The identified problems included a lack of viral load testing (41, 100%), lack of CD4 count monitoring (15; 36.6%) and lack of prophylactic treatment against opportunistic infections (10; 24.4%). Medication-related problems included the presence of clinically significant drug-drug interactions and serious side effects, CD4 count decline despite being on antiretroviral therapy, unnecessary treatment interruptions including risk for IRIS, inappropriate antiretroviral therapy regimen, non-adherence and absence of treating tuberculosis as co-morbidity. Conclusion: Present study demonstrates the need of an active antiretroviral-stewardship programme's benefits. The possible role of the clinical pharmacist as active participant and leader in this programme is highlighted. Contribution: Highlight the role of clinical pharmacists in antiretroviral stewardship.

Challenges faced by blind patients using chronic medication at a tertiary hospital in South Africa.

Background: Difficulties faced by blind patients in using medicines are largely unknown and underexplored. This limits the ability of health providers and health policy makers to plan and provide for medicine related needs of this special group. Objectives: To describe the challenges faced by blind patients around Mankweng Hospital when taking chronic medications and to identify methods used to overcome the challenges. Methods: Quantitative cross-sectional descriptive study, where questionnaires were administered to 82 blind patients, 18 years and older, and who were on chronic medications. Data was analysed using the Statistical Package for the Social Sciences (SPSS) software. Results: Majority of participants were elderly (59%) and had partial blindness (78%). Challenges faced by participants included inability to locate and identify medication (60%), missing doses (64%), inaccurate dosing and spilling medicines (33%). A staggering 68.3% of the participants did not have specific methods to overcome challenges. Conclusions: Challenges faced by the blind and visually impaired are similar across the world. However, participants are unaware of other simple, feasible methods available in the market. Current methods used by the participants to overcome the challenges encountered are minimal or caregiver dependent. Programs may be set up at clinics, hospitals and health care centers to teach the visually impaired simple and inexpensive methods to help administer medications. Contribution: Results obtained may be used to raise awareness in health care policy makers of the under-explored challenges faced by the partially blind or completely blind patients in the use of medicines.

A Comprehensive Review of Cross-Linked Gels as Vehicles for Drug Delivery to Treat Central Nervous System Disorders.

Gels are attractive candidates for drug delivery because they are easily producible while offering sustained and/or controlled drug release through various mechanisms by releasing the therapeutic agent at the site of action or absorption. Gels can be classified based on various characteristics including the nature of solvents used during preparation and the method of cross-linking. The development of novel gel systems for local or systemic drug delivery in a sustained, controlled, and targetable manner has been at the epitome of recent advances in drug delivery systems. Cross-linked gels can be modified by altering their polymer composition and content for pharmaceutical and biomedical applications. These modifications have resulted in the development of stimuli-responsive and functionalized dosage forms that offer many advantages for effective dosing of drugs for Central Nervous System (CNS) conditions. In this review, the literature concerning recent advances in cross-linked gels for drug delivery to the CNS are explored. Injectable and non-injectable formulations intended for the treatment of diseases of the CNS together with the impact of recent advances in cross-linked gels on studies involving CNS drug delivery are discussed.

Current Advances in Specialised Niosomal Drug Delivery: Manufacture, Characterization and Drug Delivery Applications.

Development of nanomaterials for drug delivery has received considerable attention due to their potential for achieving on-target delivery to the diseased area while the surrounding healthy tissue is spared. Safe and efficiently delivered payloads have always been a challenge in pharmaceutics. Niosomes are self-assembled vesicular nanocarriers formed by hydration of a non-ionic surfactant, cholesterol or other molecules that combine to form a versatile drug delivery system with a variety of applications ranging from topical delivery to targeted delivery. Niosomes have advantages similar to those of liposomes with regards to their ability to incorporate both hydrophilic and hydrophobic payloads. Moreover, niosomes have simple manufacturing methods, low production cost and exhibit extended stability, consequently overcoming the major drawbacks associated with liposomes. This review provides a comprehensive summary of niosomal research to date, including the types of niosomes and critical material attributes (CMA) and critical process parameters (CPP) of niosomes and their effects on the critical quality attributes (CQA) of the technology. Furthermore, physical characterisation techniques of niosomes are provided. The review then highlights recent applications of specialised niosomes in drug delivery. Finally, limitations and prospects for this technology are discussed.

In Vitro and In Silico Potential Inhibitory Effects of New Biflavonoids from Ochna rhizomatosa on HIV-1 Integrase and Plasmodium falciparum.

The aim of this study was to identify bioactive secondary metabolites from Ochna rhizomatosa with potential inhibitory effects against HIV and Plasmodium falciparum. A phytochemical study of O. rhizomatosa root barks resulted in the identification of three new biflavonoids (1-3), along with four known ones (4-7). Compound 7 (Gerontoisoflavone A) was a single flavonoid present in the rootbark of the plant and was used as a reference. Compound 1 (IC50 = 0.047 µM) was the only one with a noteworthy inhibitory effect against HIV-1 integrase in vitro. Chicoric acid (IC50 = 0.006 µM), a pure competitive inhibitor of HIV-1 integrase, was used as control. Compound 2 exhibited the highest antiplasmodial activity (IC50 = 4.60 µM) against the chloroquine-sensitive strain of Plasmodium falciparum NF54. Computational molecular docking revealed that compounds 1 and 2 had the highest binding score (-121.8 and -131.88 Kcal/mol, respectively) in comparison to chicoric acid and Dolutegravir (-116 and -100 Kcal/mol, respectively), towards integrase receptor (PDB:3LPT). As far as Plasmodium-6 cysteine s48/45 domain inhibition is concerned, compounds 1 and 2 showed the highest binding scores in comparison to chloroquine, urging the analysis of these compounds in vivo for disease treatment. These results confirm the potential inhibitory effect of compounds 1 and 2 for HIV and malaria treatment. Therefore, our future investigation to find inhibitors of these receptors in vivo could be an effective strategy for developing new drugs.

Lipid-Based Nanocarriers for Neurological Disorders: A Review of the State-of-the-Art and Therapeutic Success to Date.

Neurodegenerative disorders including Alzheimer's, Parkinson's, and dementia are chronic and advanced diseases that are associated with loss of neurons and other related pathologies. Furthermore, these disorders involve structural and functional defections of the blood-brain barrier (BBB). Consequently, advances in medicines and therapeutics have led to a better appreciation of various pathways associated with the development of neurodegenerative disorders, thus focusing on drug discovery and research for targeted drug therapy to the central nervous system (CNS). Although the BBB functions as a shield to prevent toxins in the blood from reaching the brain, drug delivery to the CNS is hindered by its presence. Owing to this, various formulation approaches, including the use of lipid-based nanocarriers, have been proposed to address shortcomings related to BBB permeation in CNS-targeted therapy, thus showing the potential of these carriers for translation into clinical use. Nevertheless, to date, none of these nanocarriers has been granted market authorization following the successful completion of all stages of clinical trials. While the aforementioned benefits of using lipid-based carriers underscores the need to fast-track their translational development into clinical practice, technological advances need to be initiated to achieve appropriate capacity for scale-up and the production of affordable dosage forms.

Fabrication and Characterisation of a Photo-Responsive, Injectable Nanosystem for Sustained Delivery of Macromolecules.

The demand for biodegradable sustained release carriers with minimally invasive and less frequent administration properties for therapeutic proteins and peptides has increased over the years. The purpose of achieving sustained minimally invasive and site-specific delivery of macromolecules led to the investigation of a photo-responsive delivery system. This research explored a biodegradable prolamin, zein, modified with an azo dye (DHAB) to synthesize photo-responsive azoprolamin (AZP) nanospheres loaded with Immunoglobulin G (IgG). AZP nanospheres were incorporated in a hyaluronic acid (HA) hydrogel to develop a novel injectable photo-responsive nanosystem (HA-NSP) as a potential approach for the treatment of chorio-retinal diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. AZP nanospheres were prepared via coacervation technique, dispersed in HA hydrogel and characterised via infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). Size and morphology were studied via scanning electron microscopy (SEM) and dynamic light scattering (DLS), UV spectroscopy for photo-responsiveness. Rheological properties and injectability were investigated, as well as cytotoxicity effect on HRPE cell lines. Particle size obtained was <200 nm and photo-responsiveness to UV = 365 nm by decreasing particle diameter to 94 nm was confirmed by DLS. Encapsulation efficiency of the optimised nanospheres was 85% and IgG was released over 32 days up to 60%. Injectability of HA-NSP was confirmed with maximum force 10 N required and shear-thinning behaviour observed in rheology studies. In vitro cell cytotoxicity effect of both NSPs and HA-NSP showed non-cytotoxicity with relative cell viability of ≥80%. A biocompatible, biodegradable injectable photo-responsive nanosystem for sustained release of macromolecular IgG was successfully developed.