Endoplasmic reticulum stress in pancreatic ß-cell dysfunction: The potential therapeutic role of dietary flavonoids.

Diabetes mellitus (DM) is a global health burden that is characterized by the loss or dysfunction of pancreatic ß-cells. In pancreatic ß-cells, endoplasmic reticulum (ER) stress is a fact of life that contributes to ß-cell loss or dysfunction. Despite recent advances in research, the existing treatment approaches such as lifestyle modification and use of conventional therapeutics could not prevent the loss or dysfunction of pancreatic ß-cells to abrogate the disease progression. Therefore, targeting ER stress and the consequent unfolded protein response (UPR) in pancreatic ß-cells may be a potential therapeutic strategy for diabetes treatment. Dietary phytochemicals have therapeutic applications in human health owing to their broad spectrum of biochemical and pharmacological activities. Flavonoids, which are commonly obtained from fruits and vegetables worldwide, have shown promising prospects in alleviating ER stress. Dietary flavonoids including quercetin, kaempferol, myricetin, isorhamnetin, fisetin, icariin, apigenin, apigetrin, vitexin, baicalein, baicalin, nobiletin hesperidin, naringenin, epigallocatechin 3-O-gallate hesperidin (EGCG), tectorigenin, liquiritigenin, and acacetin have shown inhibitory effects on ER stress in pancreatic ß-cells. Dietary flavonoids modulate ER stress signaling components, chaperone proteins, transcription factors, oxidative stress, autophagy, apoptosis, and inflammatory responses to exert their pharmacological effects on pancreatic ß-cells ER stress. This review focuses on the role of dietary flavonoids as potential therapeutic adjuvants in preserving pancreatic ß-cells from ER stress. Highlights of the underlying mechanisms of action are also presented as well as possible strategies for clinical translation in the management of DM.

Ethnomedicinal Uses, Phytochemistry and Pharmacological Properties of Suregada Genus: A Review.

Plants of the Suregada Roxb. ex Rottler (formerly Gelonium Roxb. ex Willd) are utilized to treat various ailments, namely, hepatic, gum diseases, pyrexia, eczema, and venereal diseases. This review links the reported compounds to ethnomedicinal uses through pharmacological activities. The compounds possess anticancer, anti-allergic, antibacterial, anti-inflammatory, antioxidant, and anti-HIV properties. From the previous reports, 32 known species of the Suregada genus have been investigated morphologically, and nine were investigated for their phytochemistry and pharmacology. Phytochemistry, ethnomedicinal, and pharmacological uses of the other 23 Suregada species are not known and/or not reported. In this review, abietane diterpenoids are the main compounds expressed by the Suregada, accounting for 71 of the 114 reported compounds. Ten triterpenoids and sterols, one aliphatic, two lignans, five flavonoids, and twenty-one nitrogen-containing compounds have been reported from the genus.

Knowledge, perceptions, practices, promotive factors, and health risks awareness of African Basotho women towards skin lightening products: a cross-sectional survey.

Introduction: the use of skin lightening products (SLPs) by women is poorly documented in Africa, with statistics from some countries entirely missing. This study assessed knowledge, perceptions, practices and factors associated with health risk awareness of African Basotho women towards SLPs. Methods: this was a questionnaire-based cross-sectional study based on convenience sampling of females in secondary/high schools, universities, factories and business offices in Maseru City, Lesotho. Analysis of the differences in knowledge (adequate ≥50% score), perceptions, and practices between four participant groups was based on ANOVA, p<0.05. Associations between sociodemographic variables and the use of SLPs were performed using logistic regression model in SPSS version 27. Results: a total of 468 participants out of 496 responders qualified for data analysis based on predefined data cleaning criteria. Knowledge about SLPs was adequate (78.2%, n=468). By proportion, the main sources of the SLPs were supermarkets (67.6%, n=183) and pharmacy stores (41.9%). About 43.7% (n=468) of the participants used SLPs, with the factory workers mostly associated with SLPs use (aOR: 2.91, 95% CI 1.15-7.40; p=0.02). The majority (53.4%, n=131) of users had inadequate knowledge about the link between skin lightening and skin problems. The most common reasons for use of SLPs were rash (pimples, blemishes) (43.9%, n=107), dry skin (41.1%) and skin reddening (33.6%). Conclusion: there was adequate knowledge and moderate practice of skin lightening among African Basotho women. Public awareness campaigns and strict regulations are required to address the problem of SLPs use.

Formulation and characterization of liposomes containing drug absorption enhancers for optimized anti-HIV and antimalarial drug delivery.

Most of the current clinically used anti-HIV and antimalarial drugs have low bioavailability, either due to poor solubility and permeability, rapid clearance from anatomical reservoirs and poor retention at their site of action (e.g. due to the p-glycoprotein efflux system), and extreme first-pass metabolism (e.g. by the cytochrome P450 enzymes). Hence, new approaches such as the incorporation of drug absorption enhancers (DAEs) (also referred to as bioenhancers) into dosage forms, and exploration of nanocarriers such as liposomes as novel dosage forms, are needed and may provide a viable means that could improve the bioavailability of both anti-HIV and antimalarial drugs. Liposomes loaded with efavirenz or mefloquine in combination with drug absorption enhancers, as well as placebo dosage forms, were prepared using a thin-lipid film hydration technique and characterized for their particle size and zeta potentials, entrapment efficiency, in vitro drug release, and in vitro drug permeability. Liposomes were further investigated for their biocompatibility (safety) using H-4-II-E liver cells in vitro. Drug-loaded liposomes prepared using l-α-phospatidylcholine, dioleoyl (DOPC) and cholesterol (CHOL) (1:1 mol/mol) as well as liposomes made of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), CHOL, and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) (4:6:26 mol/mol/mol) exhibited the best results in terms of their entrapment efficiency, particle size, zeta potential, in vitro drug release, and permeability. DSPC:CHOL:DPPC liposomes released EFV-based formulations better than DPPC:CHOL liposomes for immediate release behaviour. DOPC:CHOL liposomes produced a controlled release and more drug was released in the presence of DAEs for both EFV (0.4-fold higher) and MQ-based (sevenfold higher) formulations in the first 2 h. However, these liposomes were less biocompatible (< 50% cell viability) with liver cells. DOPC:CHOL and DSPC:CHOL:DPPC liposomes could provide a useful nano-formulation platform, which could ensure drug loading, followed by sustained release of both anti-HIV and antimalaria drugs.

Recent and advanced nano-technological strategies for COVID-19 vaccine development.

The outbreak of the COVID-19 pandemic in 2019 has been one of the greatest challenges modern medicine and science has ever faced. It has affected millions of people around the world and altered human life and activities as we once knew. The high prevalence as well as an extended period of incubations which usually does not present with symptoms have played a formidable role in the transmission and infection of millions. A lot of research has been carried out on developing suitable treatment and effective preventive measures for the control of the pandemic. Preventive strategies which include social distancing, use of masks, washing of hands, and contact tracing have been effective in slowing the spread of the virus; however, the infectious nature of the SARS-COV-2 has made these strategies unable to eradicate its spread. In addition, the continuous increase in the number of cases and death, as well as the appearance of several variants of the virus, has necessitated the development of effective and safe vaccines in a bid to ensure that human activities can return to normalcy. Nanotechnology has been of great benefit in the design of vaccines as nano-sized materials have been known to aid the safe and effective delivery of antigens as well as serve as suitable adjuvants to potentiate responses to vaccines. There are only four vaccine candidates currently approved for use in humans while many other candidates are at various levels of development. This review seeks to provide updated information on the current nano-technological strategies employed in the development of COVID-19 vaccines.

Determination of effective concentrations of drug absorption enhancers using in vitro and ex vivo models.

BACKGROUND: Achievement of an effective concentration of the pharmaceutically active ingredient in the blood and/or at the target site is an important aspect in the formulation of drugs and therefore needs to be quantified. Any concentration above therapeutic levels can cause toxic effects whereas low concentrations can be sub-therapeutic. This paper investigated different concentrations of selected commercially sourced analytical-grade pure chemicals as potential drug absorption enhancers in vitro and ex vivo to determine the lowest effective concentrations for optimizing drug absorption in oral dosage forms. METHODS: Recombinant cytochrome (CYP) 3A4 enzyme and recombinant p-glycoprotein membrane models were utilized for the investigation of in vitro inhibitory effects of drug absorption enhancers. Promega (2015) protocols were adopted for both assays. The everted porcine intestinal ex vivo model was employed for assessing effects of the drug absorption enhancers on the absorption of propranolol. RESULTS: The lowest effective CYP3A4 inhibitory concentrations were observed for curcumin (75µM and 100 µM), quercetin (75 and 100 µM) and glycyrrhizic acid (50 µM) while the most effective p-glycoprotein (P-gp) inhibition concentrations were curcumin (10, 15, 25, 50, 75 and 100 µM), sinomenine (50, 75, and 100 µM), quercetin (75 and 100 µM) and naringin (50 µM). Additive effects were observed between combinations of quercetin (75 µM) and curcumin (100 µM); quercetin (75 µM) and curcumin (75 µM); quercetin (75 µM) and curcumin (50 µM), and quercetin (75 µM) with curcumin (10 µM), which increased the basal ex vivo absorption of propranolol from 1.24 ± 0.03 µg/mL to 5.19 ± 0.12 µg/mL, 4.17 ± 0.05 µg/mL, 3.86 ± 0.10 µg/mL, and 4.07± 0.05 µg/mL respectively, after 2 hours. CONCLUSION: Incorporation of the drug absorption enhancers (e.g., curcumin and quercetin), at specific concentrations, in dosage forms could improve the bioavailability of the BCS Class III and IV drugs that are substrates of CYP3A4 and p-glycoprotein.

A 30-year bibliometric analysis of research coverage on HIV and AIDS in Lesotho.

BACKGROUND: Given the well documented undesired impacts of HIV/AIDS globally, there is a need to create a statistical inventory of research output on HIV/AIDS. This need is particularly important for a country such as Lesotho, whose HIV/AIDS prevalence is one of the highest globally. Research on HIV/AIDS in sub-Saharan Africa continues to trail behind that of other regions, especially those of the developed countries. Lesotho, a sub-Saharan country, is a developing country with lower research output in this area when longitudinally compared to other countries. This study reviewed the volume and scope of the general research output on HIV/AIDS in Lesotho and assessed the coverage of the national research agenda on HIV/AIDS, making recourse to statistical principles. METHODS: A bibliometric review of studies on HIV/AIDS retrieved from the SCOPUS and PubMed databases, published within the 30-year period between 1985 and 2016, was conducted. The focus of each of the studies was analysed and the studies were cross-matched with the national research agenda in accordance with bibliometric methodologies. RESULTS: In total, 1280 studies comprising 1181 (92.3%) journal articles, 91 (7.1%) books and 8 (0.6%) conference proceedings were retrieved. By proportion, estimation of burden of infection (40.7%) had the highest research volume, while basic (5.5%) and preventive measures (24.4%) and national planning (29.4%) had the lowest. Out of the total studies retrieved, only 516 (40.3%) matched the national research agenda. Research on maternal and child health quality of care, viral load point-of-care devices, and infant point-of-care diagnosis had hardly any publications in the high priority research category of the agenda. CONCLUSION: Notwithstanding a considerable research output on HIV/AIDS for Lesotho, there is insufficient coverage of the national research agenda in this research area. The major research gaps on general research output are in basic and preventive measures as well as national planning. There is also a need to increase targeted funding for HIV/AIDS research to appropriately address the most compelling gaps and national needs.

Effects of dietary fruits, vegetables and a herbal tea on the in vitro transport of cimetidine: comparing the Caco-2 model with porcine jejunum tissue.

CONTEXT: Dietary botanicals are often consumed together with allopathic medicines, which may give rise to pharmacokinetic interactions. In vitro intestinal models are useful to identify botanical-drug interactions, but they may exhibit different expressions of transporters or enzymes. OBJECTIVE: To compare the effects of selected dietary botanical extracts on cimetidine transport across two in vitro intestinal models. MATERIALS AND METHODS: Bi-directional transport of cimetidine was measured across Caco-2 cell monolayers and excised porcine jejunum tissue in the absence (control) as well as the presence of verapamil (positive control) and selected plant extracts. RESULTS: Sclerocarya birrea Hochst. (Anacardiaceae) (marula) and Psidium guajava L. (Myrtaceae) (guava) crude extracts significantly decreased cimetidine efflux in both in vitro models resulting in increased absorptive transport of the drug. On the other hand, Dovyalis caffra Sim. (Flacourtiaceae) (Kei-apple), Prunus persica (L.) Batsch (Rosaceae) (peach), Aspalathus linearis (Burm. f.) R. Dahlgren (Fabaceae) (rooibos tea), Daucus carota L. (Apiaceae) (carrot), Prunus domestica A. Sav. (Rosaceae) (plum), Beta vulgaris L. (Chenopodiaceae) (beetroot) and Fragaria x ananassa (Weston) Duchesne ex Rozier. (Rosaceae) (strawberry) crude extracts exhibited different effects on cimetidine transport between the two models. DISCUSSION: Caco-2 cells were more sensitive to changes in cimetidine transport by the plant extracts and therefore may overestimate the effects of co-administered plant extracts on drug transport compared to the excised pig tissue model, which is congruent with findings from previous studies. CONCLUSIONS: The excised porcine jejunum model seemed to provide a more realistic estimation of botanical-drug pharmacokinetic interactions than the Caco-2 cell model.

Moulded cross-linked chitosan matrix systems for controlled drug release.

Matrix-type drug delivery systems were prepared by moulding and drying cross-linked chitosan gels in 24-well plates and they were evaluated in terms of their physical properties, drug content, surface morphology and swelling. Furthermore, the in vitro drug release profiles were subjected to kinetic modelling at two different pH values. In general, the moulded matrix systems showed statistically significantly slower drug release compared to immediate release tablets as measured by the mean dissolution time. Drug release from the moulded matrix systems prepared from chitosan cross-linked with tripolyphosphate was pH-dependent as can be seen from the release exponent value (n) of 0.75 at pH 5.8 (anomalous transport, erosion), while the n value was only 0.40 at pH 7.4 (Fickian diffusion). The matrix systems obtained from chitosan cross-linked with sodium lauryl sulphate showed higher swelling but mostly Fickian diffusional release (n?=?0.25 at pH 7.4, n?=?0.41 at pH 5.8).

Herb-drug pharmacokinetic interactions reviewed.

IMPORTANCE OF THE FIELD: the global increase in the popularity of alternative medicines has raised renewed concerns regarding herb-drug interactions. These interactions are especially important for drugs with narrow therapeutic indices and may either be pharmacodynamic or pharmacokinetic in nature. AREAS COVERED IN THIS REVIEW: pharmacokinetic interactions which may exist between herbs and drugs, and the mechanisms of these interactions with appropriate examples based on primary and secondary data in publications are discussed. The mechanisms covered include those that affect oral drug absorption (e.g., modulation of efflux and uptake transporters, complex formation, gastrointestinal motility and pH) and drug biotransformation (e.g., inhibition or induction of enzymes). WHAT THE READER WILL GAIN: knowledge on the mechanisms of herb-drug pharmacokinetic interactions supported by an extended list of these types of interactions for quick reference. A critical evaluation of certain herb-drug pharmacokinetic interactions reported in the scientific literature. TAKE HOME MESSAGE: as the incidence and severity of herb-drug pharmacokinetic interactions increase due to a worldwide rise in the use of herbal preparations, more clinical data regarding herb-drug pharmacokinetic interactions are needed to make informed decisions regarding patient safety.