Objectives: Traumatic brain injury (TBI) is one of the top causes of morbidity and mortality worldwide. The review aimed to discuss and summarize the current evidence on the effectiveness of adjuvant neuroprotective treatments in terms of their effect on brain injury biomarkers in TBI patients. Methods: To identify relevant studies, four scholarly databases, including PubMed, Cochrane, Scopus, and Google Scholar, were systematically searched using predefined search terms. English-language randomized controlled clinical trials reporting changes in brain injury biomarkers, namely, neuron-specific enolase (NSE), glial fibrillary acid protein (GFAP), ubiquitin carboxyl-terminal esterase L1 (UCHL1) and/or S100 beta (S100 ß), were included. The methodological quality of the included studies was assessed using the Cochrane risk-of-bias tool. Results: A total of eleven studies with eight different therapeutic options were investigated; of them, tetracyclines, metformin, and memantine were discovered to be promising choices that could improve neurological outcomes in TBI patients. The most utilized serum biomarkers were NSE and S100 ß followed by GFAP, while none of the included studies quantified UCHL1. The heterogeneity in injury severity categories and measurement timing may affect the overall evaluation of the clinical efficacy of potential therapies. Therefore, unified measurement protocols are highly warranted to inform clinical decisions. Conclusion: Few therapeutic options showed promising results as an adjuvant to standard care in patients with TBI. Several considerations for future work must be directed towards standardizing monitoring biomarkers. Investigating the pharmacotherapy effectiveness using a multimodal biomarker panel is needed. Finally, employing stratified randomization in future clinical trials concerning potential confounders, including age, trauma severity levels, and type, is crucial to inform clinical decisions. Clinical Trial Registration: [https://www.crd.york.ac.uk/prospero/dis], identifier [CRD42022316327].
The objective of this study is to access the effect of purple sweet potato leaf (PSPL) extract on diabetic retinopathy (DR) of streptozotocin (STZ)-induced male Sprague-Dawley (SD) rats. In this study, rats were injected intraperitoneally with a single dose of 60 mg/kg STZ, and diabetes was confirmed on day 7. Rats were further divided into a few groups, which were then orally administered with one of the following treatments: 25 mg/kg of gliclazide (D25G), 200 mg/kg of PSPL extract (DT 200), and 400 mg/kg of PSPL extract (DT 400). However, the normal control (NS) and control group for diabetic (DNS) were given normal saline (NS) for 12 weeks. The results show that the treated group demonstrated a reduction in serum oral glucose tolerance test (OGTT) levels of DT 200 and DT 400, and an increase in the serum and retinal insulin levels, and restored oxidative stress markers in serum and retina on week 12. The PSPL extract exhibited protective effects in maintaining the kidney, liver, retina, and pancreas architecture in 400 mg/kg compared to the 200 mg/kg treated group and D25G, thereby restoring fully transparent lenses in diabetes-induced rats. In conclusion, 400 mg/kg PSPL is the most effective dose for the amelioration of STZ-induced DR pathology in male SD rats.
Head and neck squamous cell carcinoma is a disease that most commonly produce tumours from the lining of the epithelial cells of the lips, larynx, nasopharynx, mouth, or oro-pharynx. It is one of the most deadly forms of cancer. About one to two percent of all neo-plasm-related deaths are attributed to head and neck squamous cell carcinoma, which is responsible for about six percent of all cancers. MicroRNAs play a critical role in cell proliferation, differentiation, tumorigenesis, stress response, triggering apoptosis, and other physiological process. MicroRNAs regulate gene expression and provide new diagnostic, prognostic, and therapeutic options for head and neck squamous cell carcinoma. In this work, the role of molecular signaling pathways related to head and neck squamous cell carcinoma is emphasized. We also provide an overview of MicroRNA downregulation and overexpression and its role as a diagnostic and prognostic marker in head and neck squamous cell carcinoma. In recent years, MicroRNA nano-based therapies for head and neck squamous cell carcinoma have been explored. In addition, nanotechnology-based alternatives have been discussed as a promising strategy in exploring therapeutic paradigms aimed at improving the efficacy of conventional cytotoxic chemotherapeutic agents against head and neck squamous cell carcinoma and attenuating their cytotoxicity. This article also provides information on ongoing and recently completed clinical trials for therapies based on nanotechnology.
Huntington's disease (HD), a neurodegenerative disease, normally starts in the prime of adult life, followed by a gradual occurrence of psychiatric disturbances, cognitive and motor dysfunction. The daily performances and life quality of HD patients have been severely interfered by these clinical signs and symptoms until the last stage of neuronal cell death. To the best of our knowledge, no treatment is available to completely mitigate the progression of HD. Mangiferin, a naturally occurring potent glucoxilxanthone, is mainly isolated from the Mangifera indica plant. Considerable studies have confirmed the medicinal benefits of mangiferin against memory and cognitive impairment in neurodegenerative experimental models such as Alzheimer's and Parkinson's diseases. Therefore, this study aims to evaluate the neuroprotective effect of mangiferin against 3-nitropropionic acid (3-NP) induced HD in rat models. Adult Wistar rats (n = 32) were randomly allocated equally into four groups of eight rats each: normal control (Group I), disease control (Group II) and two treatment groups (Group III and Group IV). Treatment with mangiferin (10 and 20 mg/kg, p. o.) was given for 14 days, whereas 3-NP (15 mg/kg, i. p.) was given for 7 days to induce HD-like symptoms in rats. Rats were assessed for cognitive functions and motor coordination using open field test (OFT), novel object recognition (NOR) test, neurological assessment, rotarod and grip strength tests. Biochemical parameters such as oxidative stress markers and pro-inflammatory markers in brain hippocampus, striatum and cortex regions were evaluated. Histopathological study on brain tissue was also conducted using hematoxylin and eosin (H&E) staining. 3-NP triggered anxiety, decreased recognition memory, reduced locomotor activity, lower neurological scoring, declined rotarod performance and grip strength were alleviated by mangiferin treatment. Further, a significant depletion in brain malondialdehyde (MDA) level, an increase in reduced glutathione (GSH) level, succinate dehydrogenase (SDH), superoxide dismutase (SOD) and catalase (CAT) activities, and a decrease in tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) levels were observed in mangiferin treated groups. Mangiferin also mitigated 3-NP induced histopathological alteration in the brain hippocampus, striatum and cortex sections. It could be inferred that mangiferin protects the brain against oxidative damage and neuroinflammation, notably via antioxidant and anti-inflammatory activities. Mangiferin, which has a good safety profile, may be an alternate treatment option for treating HD and other neurodegenerative disorders. The results of the current research of mangiferin will open up new avenues for the development of safe and effective therapeutic agents in diminishing HD.
Zingiber and Alpinia species (family: Zingiberaceae) are popularly used in food as spices and flavoring agents and in ethnomedicine to heal numerous diseases, including immune-related disorders. However, their ethnomedicinal uses have not been sufficiently supported by scientific investigations. Numerous studies on the modulating effects of plants and their bioactive compounds on the different steps of the immune system have been documented. This review aimed to highlight up-to-date research findings and critically analyze the modulatory effects and mechanisms of the extracts and secondary compounds of several Zingiber and Alpinia species, namely, Zingiber officinale Roscoe, Z. cassumunar Roxb., Z. zerumbet (L.) Roscoe ex Sm., Alpinia galanga Linn., A. conchigera Griff, A. katsumadai Hayata, A. oxyphylla Miq., A. officinarum Hance, A. zerumbet (Pers.) Burtt. et Smith, and A. purpurata (Viell.) K. Schum. on the immune system, particularly via the inflammation-related signaling pathways. The immunomodulating activities of the crude extracts of the plants have been reported, but the constituents contributing to the activities have mostly not been identified. Among the extracts, Z. officinale extracts were the most investigated for their in vitro, in vivo, and clinical effects on the immune system. Among the bioactive metabolites, 6-, 8-, and 10-gingerols, 6-shogaol, and zerumbone from Zingiber species and cardamomin, 1'-acetoxychavicol acetate, yakuchinone, rutin, 1,8-cineole, and lectin from Alpinia species have demonstrated strong immunomodulating effects. More experimental studies using cell and animal models of immune-related disorders are necessary to further understand the underlying mechanisms, together with elaborate preclinical pharmacokinetics, pharmacodynamics, bioavailability, and toxicity studies. Many of these extracts and secondary metabolites are potential candidates for clinical development in immunomodulating agents or functional foods to prevent and treat chronic inflammatory disorders.
Alzheimer's disease (AD) is the most prevalent form of dementia affecting millions of people worldwide. It is a progressive, irreversible, and incurable neurodegenerative disorder that disrupts the synaptic communication between millions of neurons, resulting in neuronal death and functional loss due to the abnormal accumulation of two naturally occurring proteins, amyloid β (Aβ) and tau. According to the 2018 World Alzheimer's Report, there is no single case of an Alzheimer's survivor; even 1 in 3 people die from Alzheimer's disease, and it is a growing epidemic across the globe fruits and vegetables rich in glucosinolates (GLCs), the precursors of isothiocyanates (ITCs), have long been known for their pharmacological properties and recently attracted increased interest for the possible prevention and treatment of neurodegenerative diseases. Epidemiological evidence from systematic research findings and clinical trials suggests that nutritional and functional dietary isothiocyanates interfere with the molecular cascades of Alzheimer's disease pathogenesis and prevent neurons from functional loss. The aim of this review is to explore the role of glucosinolates derived isothiocyanates in various molecular mechanisms involved in the progression of Alzheimer's disease and their potential in the prevention and treatment of Alzheimer's disease. It also covers the chemical diversity of isothiocyanates and their detailed mechanisms of action as reported by various in vitro and in vivo studies. Further clinical studies are necessary to evaluate their pharmacokinetic parameters and effectiveness in humans.
The field of cancer nanotheranostics is rapidly evolving, with cyclodextrin (CD)-based nanoparticles emerging as a promising tool. CDs, serving as nanocarriers, have higher adaptability and demonstrate immense potential in delivering powerful anti-cancer drugs, leading to promising and specific therapeutic outcomes for combating various types of cancer. The unique characteristics of CDs, combined with innovative nanocomplex creation techniques such as encapsulation, enable the development of potential theranostic treatments. The review here focuses mainly on the different techniques administered for effective nanotheranostics applications of CD-associated complex compounds in the domain of cancer treatments. The experimentations on various loaded drugs and their complex conjugates with CDs prove effective in in vivo results. Various cancers can have potential nanotheranostics cures using CDs as nanoparticles along with a highly efficient process of nanocomplex development and a drug delivery system. In conclusion, nanotheranostics holds immense potential for targeted drug delivery and improved therapeutic outcomes, offering a promising avenue for revolutionizing cancer treatments through continuous research and innovative approaches.
With the advent of highly effective plant-based medications with few or no side effects, the use of phytomedicines against complex diseases such as cancer is becoming more widespread. The broadly recognized pentacyclic triterpenes known as boswellic acids (BAs) are derived from the oleogum resin, or frankincense, extracted from the plant species of the genus Boswellia. The frankincense mixture contains various BA types, each having a different potential and helping treat certain cancers. This review focuses on details regarding the traits of the BAs, their roles as anti-cancer agents, the mechanism underlying their activities, and the function of their semi-synthetic derivatives in managing and treating certain cancers. The review also explores the biological sources of BAs, how they are conserved, and how biotechnology might help preserve and improve in vitro BA production. The review concludes that the BAs and their semi-synthetic derivatives are effective against a broad spectrum of cancer cell lines. The detailed information in the review can be helpful for researchers to gain more information about BAs and BA-based medications for efficient and cost-effective cancer treatments.
Introduction: An estimated 80% of the world's population use traditional and complementary medicine (T&CM) products as part of their healthcare, with many accessed through pharmacy. This cross-cultural study posed a set of professional practice responsibilities and actions to pharmacists related to T&CM products, with a view toward developing consensus, safeguarding, and promoting the health of the public. Methods: Data were collected from 2,810 pharmacists across nine countries during 2022 via a cross-sectional online survey reported in accordance with the guidelines of STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) and the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). Results: Of the 2,810 participants from nine countries, 2,341 completed all sections of the survey. Of these, most agreed (69%) that T&CM product use was common in the community they served, but most did not have adequate training to support consumer needs. Over 75% acknowledged that there were known and unknown safety risks associated with T&CM use. Of 18 professional responsibilities posed, 92% agreed that pharmacists should be able to inform consumers about potential risks, including T&CM side effects and drug-herb interactions. The provision of accurate scientific information on the effectiveness of T&CM products, skills to guide consumers in making informed decisions, and communication with other healthcare professionals to support appropriate and safe T&CM product use were all ranked with high levels of agreement. In order to effectively fulfill these responsibilities, pharmacists agreed that regulatory reforms, development of T&CM education and training, and access to quality products supported by high-quality evidence were needed. Conclusion: General agreement from across nine countries on eighteen professional responsibilities and several stakeholder actions serve as a foundation for the discussion and development of international T&CM guidelines for pharmacists.
Background: The use of drugs containing fiscalized substances is essential in different medical areas, including pain management, obstetric emergencies, and the treatment of mental disorders. However, due to their potential for abuse and negative health effects, the dispensing of these substances demands pharmacists with the requisite skills and practice. Objective: This study assesses the skills and practices of pharmacy personnel in the United Arab Emirates (UAE) regarding the dispensing of tramadol, a medication containing fiscalized substances, in community pharmacies. Methodology: A cross-sectional study was conducted. Community Pharmacies were chosen via random sampling, and seven well-trained final year pharmacy students visited them and conducted face-to-face interviews. The survey tool covered items highlighting the demographic data of the subjects, and items on the practice and skills regarding dispensing the fiscalized substances. The content validity ratio values of all tool questions were more than 0.78, suggesting acceptable validity and the Cronbach's α of 0.75 showed as acceptable internal reliability. The primary outcome measures of interest were the skills and practice regarding dispensing Fiscalized substances. Results: A total of 612 pharmacists were recruited in the study. The average practice score was 80%. There was a statistically significant association (p < 0.05) between practices about dispensing fiscalized substances and gender, age group, pharmacy type, work experience, university of graduation, and receiving training on epilepsy and antiepileptic drugs. Conclusion: The results implied that competency and experience are vital factors for the dispensing of tramadol. Contextually, the majority of the pharmacists evidently have the requisite competencies to provide high-quality and proper medical care, with regards to dispensing tramadol, which will minimize drug abuse and medication errors, and assist outpatients to manage their drugs containing fiscalized substances.
Background: Community pharmacists play an intermediary role between prescribing physicians and patients in the United Arab Emirates (UAE) and thus are responsible for ensuring that patients receive optimal cardiovascular disease (CVD) pharmaceutical care. Methods: we used a cross-sectional design to assess the perceptions and practices of community pharmacists concerning pharmaceutical care for patients with CVD. A trained researcher visited randomly selected community pharmacies and used a structured questionnaire to conduct in-person interviews with pharmacists. The questionnaire collected demographic data and information on perceptions and practices regarding CVD pharmaceutical care. Results: Five hundred and fifty-one participants were recruited. The average participant age (mean ± SD) was 35 ± 2.7 years. The average perception score regarding CVD prevention and management was 75.6% (95% confidence interval [CI] 77.1%-74.2%), and the average practice score for CVD prevention and management was 87.1% (95% CI 76.5%-79.6%). Bivariate analysis revealed that gender (p = 0.001), education level (p < 0.001), pharmacy position (p = 0.004), work experience (p < 0.001), number of patients served per day (p < 0.001) and being trained on CVD prevention and management (p < 0.001) were significantly associated with perceptions about the prevention and management of CVD. Better practice scores were seen among older participants (OR 1.01; 95% CI 1-1.019), postgraduates (OR 1.77; 95% CI 1.66-1.89), workers at chain pharmacies (OR 1.24; 95% CI 1.11-1.39), pharmacists in charge (OR 1.22; 95% CI 1.01-1.47), pharmacists with >10 years of experience (OR 11.3; 95% CI 6.01-15.62), pharmacists with 6-10 years of experience (OR 4.42; 95% CI 3.90-5) and pharmacists trained on CVD prevention and management (OR 1.29; 95% CI 1.15-1.46). Conclusion: Pharmacy practitioners working in community pharmacies in the UAE actively engage in delivering pharmaceutical care to patients, playing a role in CVD management and prevention. However, they showed low levels of involvement in other healthcare services, specifically in screening and measuring patients' weight, glucose levels, and blood pressure, monitoring treatment responses, maintaining medical records, and reviewing medication refill histories. Activities such as educating patients, providing medication counseling, offering support for treatment adherence, and fostering collaborative relationships with other healthcare providers should be encouraged among UAE community pharmacists to ensure the provision of high-quality patient care.
Zingiber zerumbet (L) Smith is part of the Zingiberaceae family, one of the largest families of the plant kingdom. Z. zerumbet is a perennial, aromatic and tuberose plant that grows in humid locations where its center of distribution is located in the South-East Asia region. This plant has been traditionally used in foods and beverages and for ornamental purposes. Although many studies have reported on the biomedical applications of Z. zerumbet, the anti-allergic effects of Z. zerumbet and its major bioactive compounds have not yet been summarized in detail. Many major metabolites that have been reported to contain anti-allergic properties are terpene compounds which can be found in the essential oil extracted from the rhizomes of Z. zerumbet, such as zerumbone, limonene, and humulene. The rhizome is among the part of Z. zerumbet that has been widely used for many studies due to its exceptional biomedical applications. Most of these studies have shown that the essential oil, which can be obtained through hydro-distillation of the rhizomes from Z. zerumbet, is enriched with various active metabolites. Therefore, this mini-review provides an overview of the main aspects related to the anti-allergic and immunomodulatory properties of the major bioactive compounds found in the essential oils extracted from the rhizomes of Z. zerumbet, with the aim of demonstrating the importance of essential oil extracted from the rhizomes of Z. zerumbet and its bioactive compounds in the treatment of allergy and allergy-related diseases, in addition to other widely reported and extensively studied biomedical applications.
Unresolved inflammation is a pathological consequence of persistent inflammatory stimulus and perturbation in regulatory mechanisms. It increases the risk of tumour development and orchestrates all stages of tumorigenesis in selected organs. In certain cancers, inflammatory processes create the appropriate conditions for neoplastic transformation. While in other types, oncogenic changes pave the way for an inflammatory microenvironment that leads to tumour development. Of interest, hallmarks of tumour-promoting and cancer-associated inflammation are striking similar, sharing a complex network of stromal (fibroblasts and vascular cells) and inflammatory immune cells that collectively form the tumour microenvironment (TME). The cross-talks of signalling pathways initially developed to support homeostasis, change their role, and promote atypical proliferation, survival, angiogenesis, and subversion of adaptive immunity in TME. These transcriptional and regulatory pathways invariably contribute to cancer-promoting inflammation in chronic inflammatory disorders and foster "smouldering" inflammation in the microenvironment of various tumour types. Besides identifying common target sites of numerous cancer types, signalling programs and their cross-talks governing immune cells' plasticity and functional diversity can be used to develop new fate-mapping and lineage-tracing mechanisms. Here, we review the vital molecular mechanisms and pathways that establish the connection between inflammation and tumour development, progression, and metastasis. We also discussed the cross-talks between signalling pathways and devised strategies focusing on these interaction mechanisms to harness synthetic lethal drug combinations for targeted cancer therapy.
Introduction: Hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) enzymes are major therapeutic targets of anemia and ischemic/hypoxia diseases. To overcome safety issues, liver failure, and problems associated with on-/off-targets, natural products due to their novel and unique structures offer promising alternatives as drug targets. Methods: In the current study, the Marine Natural Products, North African, South African, East African, and North-East African chemical space was explored for HIF-PHD inhibitors discovery through molecular search, and the final hits were validated using molecular simulation and free energy calculation approaches. Results: Our results revealed that CMNPD13808 with a docking score of -8.690 kcal/mol, CID15081178 with a docking score of -8.027 kcal/mol, CID71496944 with a docking score of -8.48 kcal/mol and CID11821407 with a docking score of -7.78 kcal/mol possess stronger activity than the control N-[(4-hydroxy-8-iodoisoquinolin-3-yl)carbonyl]glycine, 4HG (-6.87 kcal/mol). Interaction analysis revealed that the target compounds interact with Gln239, Tyr310, Tyr329, Arg383 and Trp389 residues, and chelate the active site iron in a bidentate manner in PHD2. Molecular simulation revealed that these target hits robustly block the PHD2 active site by demonstrating stable dynamics. Furthermore, the half-life of the Arg383 hydrogen bond with the target ligands, which is an important factor for PHD2 inhibition, remained almost constant in all the complexes during the simulation. Finally, the total binding free energy of each complex was calculated as CMNPD13808-PHD2 -72.91 kcal/mol, CID15081178-PHD2 -65.55 kcal/mol, CID71496944-PHD2 -68.47 kcal/mol, and CID11821407-PHD2 -62.06 kcal/mol, respectively. Conclusion: The results show the compounds possess good activity in contrast to the control drug (4HG) and need further in vitro and in vivo validation for possible usage as potential drugs against HIF-PHD2-associated diseases.
Periodontitis is an oral inflammatory process involving the periodontium, which is mainly caused by the invasion of periodontopathogenic microorganisms that results in gingival connective tissue and alveolar bone destruction. Metabolic products of the oral pathogens and the associated host immune and inflammatory responses triggered are responsible for the local tissue destruction. Numerous studies in the past decades have demonstrated that natural polyphenols are capable of modulating the host inflammatory responses by targeting multiple inflammatory components. The proposed mechanism by which polyphenolic compounds exert their great potential is by regulating the immune cell, proinflammatory cytokines synthesis and gene expression. However, due to its low absorption and bioavailability, the beneficial effects of these substances are very limited and it hampers their use as a therapeutic agent. To address these limitations, targeted delivery systems by nanoencapsulation techniques have been explored in recent years. Nanoencapsulation of polyphenolic compounds with different carriers is an efficient and promising approach to boost their bioavailability, increase the efficiency and reduce the degradability of natural polyphenols. In this review, we focus on the effects of different polyphenolic substances in periodontal inflammation and to explore the pharmaceutical significance of polyphenol-loaded nanoparticles in controlling periodontitis, which may be useful for further enhancement of their efficacy as therapeutic agents for periodontal disease.
Background: Countries across Africa and Asia have introduced a variety of measures to prevent and treat COVID-19 with medicines and personal protective equipment (PPE). However, there has been considerable controversy surrounding some treatments including hydroxychloroquine where the initial hype and misinformation led to shortages, price rises and suicides. Price rises and shortages were also seen for PPE. Such activities can have catastrophic consequences especially in countries with high co-payment levels. Consequently, there is a need to investigate this further. Objective: Assess changes in utilisation, prices, and shortages of pertinent medicines and PPE among African and Asian countries since the start of pandemic. Our approach: Data gathering among community pharmacists to assess changes in patterns from the beginning of March until principally the end of May 2020. In addition, suggestions on ways to reduce misinformation. Results: One hundred and thirty one pharmacists took part building on the earlier studies across Asia. There were increases in the utilisation of principally antimalarials (hydroxychloroquine) and antibiotics (azithromycin) especially in Nigeria and Ghana. There were limited changes in Namibia and Vietnam reflecting current initiatives to reduce inappropriate prescribing and dispensing of antimicrobials. Encouragingly, there was increased use of vitamins/immune boosters and PPE across the countries where documented. In addition, generally limited change in the utilisation of herbal medicines. However, shortages have resulted in appreciable price increases in some countries although moderated in others through government initiatives. Suggestions in Namibia going forward included better planning and educating patients. Conclusion: Encouraging to see increases in the utilisation of vitamins/immune boosters and PPE. However, concerns with increased utilisation of antimicrobials needs addressing alongside misinformation, unintended consequences from the pandemic and any appreciable price rises. Community pharmacists and patient organisations can play key roles in providing evidence-based advice, helping moderate prices through improved stock management, and helping address unintended consequences of the pandemic.