Exploring the Potential of Rosemary Derived Compounds (Rosmarinic and Carnosic Acids) as Cancer Therapeutics: Current Knowledge and Future Perspectives.

Cancer is a global health challenge with high morbidity and mortality rates. However, conventional cancer treatment methods often have severe side effects and limited success rates. In the last decade, extensive research has been conducted to develop safe, and efficient alternative treatments that do not have the limitations of existing anticancer medicines. Plant-derived compounds have shown promise in cancer treatment for their anti-carcinogenic and anti-proliferative properties. Rosmarinic acid (RA) and carnosic acid (CA) are potent polyphenolic compounds found in rosemary (Rosmarinus officinalis) extract. They have been extensively studied for their biological properties, which include anti-diabetic, anti-inflammatory, antioxidant, and anticancer activities. In addition, RA and CA have demonstrated effective anti-proliferative properties against various cancers, making them promising targets for extensive research to develop candidate or leading compounds for cancer treatment. This review discusses and summarizes the anti-tumor effect of RA and CA against various cancers and highlights the involved biochemical and mechanistic pathways.

NAFLD and nutraceuticals: a review of completed phase III and IV clinical trials.

Background: Nonalcoholic Fatty Liver Disease (NAFLD) has become a significant public health concern, affecting approximately one-fourth of the population. Despite its prevalence, no FDA-approved drug treatments specifically target NAFLD. Aim: To provide a review of clinical trials investigating the use of herbal remedies and dietary supplements in NAFLD management, utilizing the ClinicalTrials.gov database. Methods: This review evaluates the current evidence by examining completed phase III and IV clinical trials registered on ClinicalTrials.gov. An exhaustive search was performed on April 17, 2023, using the terms "Nonalcoholic Fatty Liver Disease" and "NAFLD." Two independent reviewers appraised eligible trials based on pre-defined inclusion and exclusion criteria. Results: An initial search yielded 1,226 clinical trials, with 12 meeting the inclusion criteria after filtration. The majority of trials focused on Omega-3 fatty acids (20.0%) and vitamin D (26.7%), followed by caffeine, chlorogenic acid, ginger, phosphatidylcholine, Trigonella Foenum-graecum seed extract, vitamin C, and vitamin E (each 6.7%). Most studies were Phase 3 (75.0%) and used a parallel assignment model (91.7%). Quadruple masking was the most prevalent technique (58.3%), and Iran was the leading country in terms of trial locations (25.0%). These interventions constitute two herbal interventions and nine supplement interventions. Conclusion: This reveals a diverse range of nutraceuticals, with Omega-3 fatty acids and vitamin D being predominant in the management of NAFLD. The global distribution of trials highlights the widespread interest in these therapeutics. However, more rigorous, large-scale trials are needed to establish safety, efficacy, and optimal dosages.

In vitro and In vivo study targeting the development of Unani Antidermatophytic Cream: Implication of Herbal Formulations in Treatment of Dermatophytosis.

Panwad (Cassia tora L.), Sarshaf (Brassica nigra L.) and Kunjad (Sesamum indicum L.) have been used in the treatment of ringworm infection since ancient times and are documented in classical literature of Unani Medicine. These plant drugs give promising results when used topically in the form of paste (zimad). Hence, the development and evaluation of a cream containing extracts of Tukhm-e-Panwad (Cassia tora L.), Sarshaf (Brassica nigra L.), and Kunjad (Sesamum indicum L.) was carried out to get better efficacy of the drugs. A total of 16 batches (F1-F16) of cream were prepared by adding varying concentrations of hydro-alcoholic extract of the drugs (20%, 40% and 50%) in water removable bases, and three batches were selected as final batches (F4-20%, F6-40% and F16-50%). In vitro antidermatophytic activity was conducted to optimize MIC against dermatophytosis-causing fungi. Dermal irritation of the prepared cream was determined in New Zealand Albino Rabbits. In vivo testing of the different concentrations of the prepared cream (20%, 40%, and 50%) was also carried out using Wistar rats to assess the antidermatophytic activity. Final batches showed good results in all the tested parameters and significant in vitro and in vivo antifungal activity in a dose-dependent manner. No microbial growth was seen in the prepared formulation. The study revealed significant antidermatophytic activity of the prepared cream against dermatophytosis-causing fungi. Hence, it can be concluded that the prepared cream can be an alternative topical agent with safe and effective antifungal activity for treating dermatophytosis.

Desmodin and isopongachromene as potential inhibitors of cyclin-dependent kinase 5: phytoconstituents targeting anticancer and neurological therapy.

Cyclin-dependent kinase 5 (CDK5) is a proline-directed serine-threonine protein kinase vital for neuronal cell cycle arrest and differentiation. It activates by binding with p35 and p39 and is important for the functioning of the nervous system. A growing body of evidence suggests that CDK5 contributes to the onset and progression of neurodegeneration and tumorigenesis and represents itself as a potential therapeutic target. Our research illustrates virtual screening of phytochemicals from the IMPPAT (Indian Medicinal Plants, Phytochemistry and Therapeutics) library to search for potential inhibitors of CDK5. Initially, the compounds from the parent library were filtered out via their physicochemical properties following the Lipinski rule of five. Then sequentially, molecular docking-based virtual screening, PAINS filter, ADMET, PASS analysis, and molecular dynamics (MD) simulation were done using various computational tools to rule out adversities that can cause hindrances in the identification of potential inhibitors of CDK5. Finally, two compounds were selected via the extensive screening showing significant binding with CDK5 ATP-binding pocket and ultimately were selected as potent ATP-competitive inhibitors of CDK5. Finally, we propose that the elucidated compounds Desmodin and Isopongachromene can be used further in the drug discovery process and act as therapeutics in the medical industry to treat certain complex diseases, including cancer and neurodegeneration.Communicated by Ramaswamy H. Sarma.

Mechanistic Insight into the Binding of Huperzine a with Human Transferrin: Computational, Spectroscopic and Calorimetric Approaches.

Huperzine A (HupA), an alkaloid found in the club moss Huperzia Serrata, has been in use for centuries in Chinese traditional medicine to treat dementia owing to its ability to inhibit the cholinergic enzyme acetylcholinesterase (AChE), thus acting as an acetylcholinesterase inhibitor (AChEI). An imbalance of metal ions in the brain is linked to Alzheimer's disease (AD) pathology. Transferrin (Tf) is a crucial player in iron homeostasis, thus highlighting its significance in AD. This study explores the plausible binding of HupA with Tf using molecular docking, molecular dynamics (MD) simulation, and free energy landscape (FEL) analyses. The docking results show that HupA binds to the functionally active region of Tf by forming three hydrogen bonds with Thr392, Glu394, and Ser688 and several hydrophobic interactions. The MD simulation analyses show that HupA binding is stable with Tf, causing minimal changes to the protein conformation. Moreover, principal component analysis (PCA) and FEL also depict the stable binding of HupA with Tf without any significant fluctuations. Further, fluorescence-based binding suggested excellent binding affinity of HupA with Tf affirming in silico observations. Isothermal titration calorimetry (ITC) advocated the spontaneous binding of HupA with Tf. This study provides an insight into the binding mechanism of HupA with Tf, and overall, the results show that HupA, after required experimentations, can be a better therapeutic agent for treating AD while targeting Tf.

Screening and Determination of Synthetic PDE-5 Inhibitors in Adulterated Sexual Enhancement Supplements.

This paper reports an important investigation and quantification of adulteration of sexual enhancement supplements with prescription medicines available in United Arab Emirates (UAE): tadalafil, sildenafil and vardenafil. A total of 158 sexual enhancement supplements were collected and analyzed in the current study. The samples were screened using REVERSE-phase liquid chromatography tandem high-resolution mass spectrometry/mass spectrometry (RP-HPLC-MS/MS). Of all sexual enhancements, 12.7% (95% CI: 7.4-18) contained undeclared sildenafil, 3.8% (95% CI: 0.78-6.81) contained undeclared tadalafil and 1.9% (95% CI: 0.25-4.05) contained undeclared vardenafil. Of all sexual enhancement supplements, 13.9% (95% CI: 8.5-19.4) contained significant concentrations of sildenafil, tadalafil or vardenafil. While the study found relatively low levels of undeclared pharmaceutical ingredients in the sexual enhancement dietary supplements available on the UAE market, it is likely that patients with ED tend to consume multiple such supplements daily, thereby exposing themselves to highly elevated cumulative levels.

Development and Validation of a Tool to Improve Community Pharmacists' Surveillance Role in the Safe Dispensing of Herbal Supplements.

Background: There has been an appreciable increase in the use of herbal supplements, including immune boosters, during the current COVID-19 pandemic. However, there are concerns with falsified herbal supplements. Objectives: Developed a new questionnaire that can potentially help community pharmacists identify the extent of falsified herbal supplements. Methods: A 9-month cross sectional study was conducted among 500 community pharmacies across United Arab Emirates. A new 5-factor, 24-itmes scale was developed based on current labelling requirements across countries and piloted. This included seven items on identified uses and contraindication, seven items on hazard identification, four items on product identity, three items on packaging and product insert and three items on product handling and storage. The face and content validity of the scale was assessed via the content validity index (CVI). Its construct validity was tested using an exploratory factor analysis (EFA) via principally component analysis (PCA). The model was subsequently confirmed through partial confirmatory factor analysis (PCFA). Its reliability was assessed via test-retest reliability, internal consistency, item internal consistency (IIC), and intraclass correlation coefficients (ICCs). Results: The CVI of the finalized questionnaire was 0.843. The Kaiser-Meyer-Olkin measure of sampling adequacy was 0.891, and Bartlett's test of sphericity indicated significance (p-value < 0.001). Confirmation of the subsequent 5-domains was achieved through PCFA using maximum likelihood analysis with oblimin rotation. The PCFA obtained values was 0.962 for NFI, 0.977 for CFI, and 0.987 for the Tucker Lewis Index. All values were greater than 0.95, and the RMSEA value was 0.03 (i.e., less than 0.06). Consequently, the model had a good fit. All domains demonstrated Cronbach's alpha coefficients above 0.70, with 0.940 for the full instrument. Meanwhile, all items met the IIC correlation standard of ≥0.40. The instrument presented good ICC statistics of 0.940 (0.928-0.950) as well as statistical significance (p < 0.001). Community pharmacists with more than 10 experience years were more likely to identify falsified herbal supplements compared to those with 1-10 years experience (p < 0.001). Conclusion: This study developed and validated a new instrument to identify safe herbal supplements, which should enhance the role of the community pharmacists in the safe and effective treatment of suitable patients with herbal supplements.

Adulteration of Weight Loss Supplements by the Illegal Addition of Synthetic Pharmaceuticals.

Weight loss supplements that have illegal additives of pharmaceutical drugs or analogues have additional health risks, and customers may not be aware of what they are taking. This research is an essential investigation and quantification of illegally added pharmaceuticals or prescription medications, specifically fluoxetine, phenolphthalein, and sibutramine, in herbal weight loss supplements offered for sale in the United Arab Emirates (UAE). In this case, 137 weight loss supplements were collected and analyzed in this study. Reversed-phase high-performance liquid chromatography with UV absorption detection coupled to tandem mass spectrometry (RP-HPLC-MS/MS) analyses were used to determine the presence of the pharmaceutical chemicals. Among the weight loss supplements, 15.3% (95% CI: 9.2-21.4) contained undeclared sibutramine, 13.9% (95% CI: 8.01-19.7) contained undeclared phenolphthalein, and 5.1% (95% CI: 1.4-8.8) contained undeclared fluoxetine. Amongst all weight loss supplements, 17.5% (95% CI: 11.07-24) contained significant concentrations of either sibutramine, phenolphthalein, or fluoxetine. Whilst weight loss herbal supplements offered for sale in the UAE have relatively low percentages of undeclared pharmaceuticals, many people take several different supplements daily and may encounter quite high levels of combined exposure to toxic compounds.

Fish oil supplements, oxidative status, and compliance behaviour: Regulatory challenges and opportunities.

BACKGROUND: Fish oil supplements that are rich in omega-3 long-chain polyunsaturated fatty acids (n-3 PUFAs). PUFAs are among the most widely-used dietary supplements globally, and millions of people consume them regularly. There have always been public concerns that these products should be guaranteed to be safe and of good quality, especially as these types of fish oil supplements are extremely susceptible to oxidative degradation. OBJECTIVES: The aim of the current study is to investigate and examine the oxidation status of dietary supplements containing fish oils and to identify important factors related to the oxidation status of such supplements available in the United Arab Emirates (UAE). METHODS: A total of 44 fish oil supplements were analysed in this study. For each product, the oxidative parameters peroxide value (PV), anisidine value (AV), and total oxidation (TOTOX) were calculated, and comparisons were made with the guidelines supplied by the Global Organization for EPA and DHA Omega-3s (GOED). Median values for each of the above oxidative parameters were tested using the Kruskal-Wallis and Mann-Whitney U tests. P values < 0.05 were chosen as the statistically significant boundary. RESULTS: The estimate for the average PV value was 6.4 with a 95% confidence interval (CI) [4.2-8.7] compared to the maximum allowable limit of 5 meq/kg. The estimate for the average P-AV was 11 with a 95% CI [7.8-14.2] compared to the maximum allowable limit of 20. The estimate for the average TOTOX value was 23.8 meq/kg with a 95% CI [17.4-30.3] compared to the maximum allowable limit of 26 according to the GOED standards. CONCLUSION: This research shows that most, although not all, of the fish oil supplements tested are compliant with the GOED oxidative quality standards. Nevertheless, it is clear that there should be a high level of inspection and control regarding authenticity, purity, quality, and safety in the processes of production and supply of dietary supplements containing fish oils.

Heavy Metal contamination of Dietary Supplements products available in the UAE markets and the associated risk.

A specific safety concern is the possibility that a dietary supplement could be contaminated with heavy metals. This research was undertaken to investigate the daily exposure levels of heavy metals in dietary supplements available in the UAE and to explore the factors associated with the contamination of dietary supplements with heavy metals. A total of 277 dietary supplement samples were collected from the UAE market and prepared for the analysis of selected heavy metal contamination. Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the presence of heavy metals. The average daily intake of cadmium was 0.73 µg [95% CI 0.61-0.85], compared to the acceptable daily intake (ADI) of 6 µg; the daily intake of lead was 0.85 µg [95% CI 0.62-1.07], compared to the acceptable daily intake (ADI) of 20 µg; and the daily intake of arsenic was 0.67 µg [95% CI 0.57-0.78], compared to the acceptable daily intake of 10 µg. Although the dietary supplements available in the UAE have low levels of heavy metal contamination, numerous individuals are consuming a number of different dietary supplements every day and thereby may experience a cumulative level of toxic exposure. Dietary supplements formulations (Categories), dosage forms and country of origin are strong determents of heavy metal contamination in dietary supplements products.

Suboptimal Health, Dietary Supplementation, and Public Health Approaches to Regulatory Challenges in Dubai.

Objectives: Presently, limited data are available on dietary supplements (DSs) and their associated effects on health status although the consumption of DS continues to expand. This study is aimed to explore the possible relationship between DSs consumption and suboptimal health status (SHS) in Dubai, United Arab Emirates (UAE). Methods: This study was a cross-sectional research held among a sample of citizens and residents in the Emirate of Dubai in the UAE using a well-structured, self-administered, anonymous survey. Frequency tables, odds ratios, and confidence intervals were generated during the data analysis using SPSS version 23. Results: A total of 618 participants were enrolled in this study and fully completed the questionnaire. In this study, 317 participants (51.3%) (95% CI: 47.3%-55.3%) reported the use of DS products. A significant association between DS consumption and suboptimal health status was detected (P < .001). DS consumers had a 1.5-fold increased odds of suboptimal health status when compared with non-DS consumers (95% CI 1.4-1.7). Conclusion: The findings of this study suggest a need to develop policies and programs that will help minimize the risk of possible adverse events that are associated with the utilization of DSs.

Effect of khat, its constituents and restraint stress on free radical metabolism of rats.

The leaves of khat (Catha edulis) are found to have stimulating and pleasurable effect and are chewed habitually by people of East Africa and Arabian Peninsula. Due to various toxic and psychostimulative effect of khat the present study was undertaken to evaluate the effect of intragastric khat alone or its major constituents flavonoids/alkaloids administration and before and after 4 h of immobilization stress in terms of alteration of free radical scavenging/metabolizing enzymes, uric acid and glucose in rats. Oral khat, alkaloid administration or 4 h restraint stress resulted in the decrease of the circulating levels of superoxide dismutase, catalase, glutathione-S-transferase and glucose with enhanced uric acid concentrations as compared with control rats. Oral treatment with flavonoid fraction of khat was found to enhance the activities of GST and catalase but showed no effect on SOD while the level of glucose was decreased and uric acid increased. The levels of these biochemical parameters were more altered in post stress khat/alkaloid treated rats than pre stress khat/alkaloid treated rats. The alteration in the levels of SOD, GST, catalase and uric acid in the pre stress khat treated rats were comparable with that of khat alone, except the level of glucose which was further decreased in pre stress khat treated rats. The flavonoid fraction of khat reduced the stress induced oxidative stress in terms of above mentioned biochemical parameters. The present study suggests that khat alone or khat/alkaloid consumption preceding stress may significantly decrease the levels of free radical metabolizing/scavenging enzymes and glucose leading to enhanced free radical concentration and toxicity of khat, which could be due to its alkaloid fraction as flavonoids were found to show antioxidant properties for oxidative stress generated during restraint stress.