Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) protein aggregates, leading to synaptic dysfunction and neuronal cell death. In this study, we used a comprehensive approach encompassing in vitro assays, computational analyses, and an in vivo Caenorhabditis elegans model to evaluate the inhibitory effects of various xanthones, focusing on Garcinone D (GD), on Aβ42 oligomer formation. Dot blot analysis revealed concentration-dependent responses among xanthones, with GD consistently inhibiting Aβ42 oligomer formation at low concentrations (0.1 and 0.5 μM, inhibitions of 84.66 ± 2.25% and 85.06 ± 6.57%, respectively). Molecular docking and dynamics simulations provided insights into the molecular interactions between xanthones and Aβ42, highlighting the disruption of key residues involved in Aβ42 aggregation. The neuroprotective potential of GD was established using transgenic C. elegans GMC101, with substantial delays in paralysis reported at higher concentrations. Our findings show that GD is a potent suppressor of Aβ42 oligomer formation, suggesting its potential as a therapeutic candidate for AD. The concentration-dependent effects observed in both in vitro and in vivo models underscore the need for nuanced dose-response assessments. These findings contribute novel insights into the therapeutic landscape of xanthones against AD, emphasizing the multifaceted potential of GD for further translational endeavors in neurodegenerative disorder research.
Background: Effectiveness of pharmacist-led educational interventions on self-care activities and glycemic control of type 2 diabetes mellitus (T2DM) patients is vague. The purpose of this review is to appraise the effect of pharmacist-led educational interventions on self-care activities and levels of glycated hemoglobin of T2DM patients.
Methods: Five electronic databases were searched from date of database inception to September 2017. Randomized clinical trials examining the effectiveness of pharmacist-led educational interventions, directed at T2DM patients only, were included for systematic review and meta-analysis. The protocol is available with PROSPERO (CRD42017078854).
Results: Eleven studies, involving n=1,544 T2DM patients, were included in this systematic review. Meta-analysis demonstrated that pharmacist-led interventions had a significant effect on lowering of the levels of glycated hemoglobin (-0.66; 95% CI [-0.83, -0.50]; I2=58.3%; P=0.008), in comparison to usual care. Self-care activities were assessed by using Summary of Diabetes Self-care Activities tool in eight studies. Overall meta-analysis of self-care activities for included studies demonstrated a significant effect of pharmacist-led interventions on improvement of self-monitoring of blood glucose (1.62; 95% CI [0.92, 2.32]; I2=70.5%; P=0.005), foot care (1.20; 95% CI [0.49, 1.90]; I2=95.0%; P<0.001), and overall diet (1.16; 95% CI [0.38, 1.93]; I2=64.2%; P=0.094).
Conclusion: The findings of this review demonstrate a significantly positive effect of pharmacist-led educational interventions on HbA1c levels and self-care practices among T2DM patients.
Objective: This study aimed to qualitatively explore perspectives, practices, and barriers to self-care practices (eating habits, physical activity, self-monitoring of blood glucose, and medicine intake behavior) in urban Pakistani adults with type 2 diabetes mellitus (T2DM). Methods: Pakistani adults with T2DM were recruited from the outpatient departments of two hospitals in Lahore. Semistructured interviews were conducted and audiorecorded until thematic saturation was reached. Two researchers thematically analyzed the data independently using NVivo® software with differences resolved by a third researcher. Results: Thirty-two Pakistani adults (aged 35-75 years, 62% female) participated in the study. Six themes were identified from qualitative analysis: role of family and friends, role of doctors and healthcare, patients' understanding about diabetes, complication of diabetes and other comorbidities, burden of self care, and life circumstances. A variable experience was observed with education and healthcare. Counseling by healthcare providers, family support, and fear of diabetes-associated complications are the key enablers that encourage study participants to adhere to diabetes-related self-care practices. Major barriers to self care are financial constraints, physical limitations, extreme weather conditions, social gatherings, loving food, forgetfulness, needle phobia, and a hectic job. Conclusion: Respondents identified many barriers to diabetes self care, particularly related to life situations and diabetes knowledge. Family support and education by healthcare providers were key influencers to self-care practices among Pakistani people with diabetes.
In particular, neuropathic pain is a major form of chronic pain. This type of pain results from dysfunction or lesions in the central and peripheral nervous system. Capsaicin has been traditionally utilized as a medicine to remedy pain. However, the effectiveness and safety of this practice is still elusive. Therefore, this systematic review aimed to investigate the effect of topical capsaicin as a pain-relieving agent that is frequently used in pain management. In brief, all the double-blinded, randomized placebo- or vehicle-controlled trials that were published in English addressing postherpetic neuralgia were included. Meta-analysis was performed using Revman(®) version 5.3. Upon application of the inclusion and exclusion criteria, only six trials fulfilled all the criteria and were included in the review for qualitative analysis. The difference in mean percentage change in numeric pain rating scale score ranges from -31 to -4.3. This demonstrated high efficacy of topical capsaicin application and implies that capsaicin could result in pain reduction. Furthermore, meta-analysis was performed on five of the included studies. All the results of studies are in favor of the treatment using capsaicin. The incidence of side effects from using topical capsaicin is consistently higher in all included studies, but the significance of safety data cannot be quantified due to a lack of p-values in the original studies. Nevertheless, topical capsaicin is a promising treatment option for specific patient groups or certain neuropathic pain conditions such as postherpetic neuralgia.
There are various studies that have addressed the use of Cyclosporine among patients with acute myocardial infarction (AMI). However, to date there is hardly any concise and systematically structured evidence that debate on the efficacy and safety of Cyclosporine in AMI patients. The aim of this review is to systematically summarize the overall evidence from published trials, and to conduct a meta-analysis in order to determine the efficacy and safety of Cyclosporine vs. placebo or control among patients with AMI. All randomized control trial (RCT) published in English language from January 2000 to August 2017 were included for the systematic review and meta-analysis. A total of six RCTs met the inclusion and were hence included in the systematic review and meta-analysis. Based on the performed meta-analysis, no significant difference was found between Cyclosporine and placebo in terms of left ventricular ejection fraction (LVEF) improvement (mean difference 1.88; 95% CI -0.99 to 4.74; P = 0.2), mortality rate (OR 1.01; 95% Cl 0.60 to 1.67, P = 0.98) and recurrent MI occurrence (OR 0.65; 95% Cl 0.29 to 1.45, P = 0.29), with no evidence of heterogeneity, when given to patients with AMI. Cyclosporine also did not significantly lessen the rate of rehospitalisation in AMI patients when compared to placebo (OR 0.91; 95% Cl 0.58 to 1.42, P = 0.68), with moderate heterogeneity (I2 = 46%). There was also no significant improvement in heart failure events between Cyclosporine and placebo in AMI patients (OR 0.63; 95% Cl 0.31 to 1.29, P = 0.21; I2 = 80%). No serious adverse events were reported in Cyclosporine group across all studies suggesting that Cyclosporine is well tolerated when given to patients with AMI. The use of Cyclosporine in this group of patients, however, did not result in better clinical outcomes vs. placebo at improving LVEF, mortality rate, recurrent MI, rehospitalisation and heart failure event.
National immunization program of Pakistan does not include Influenza vaccines. The low rate of immunization might be attributed to the poor knowledge of influenza vaccination in Pakistan. Current study was aimed to assess the knowledge and attitude of influenza vaccination among parents. A questionnaire-based cross sectional study was conducted among randomly selected parents with at least one child aged >6 months. The responses were recorded against 27 items questionnaire assessing knowledge, perception, attitude and behaviours of parents. Data were analysed by using appropriate statistical methods. A total 532 responses were recorded with male gender preponderance (65%). Most of the parents (61.1%) reported that their children had received or planned to receive all recommended vaccines in Expanded Program on Immunization (EPI) of Pakistan. Only one third of the parents (24.4%) were aware of the availability of influenza vaccines in Pakistan, and very few (6.6%) reported vaccinating their child against influenza. Exploring the parents' attitudes regarding children vaccination, the top motivator was 'immunization is important to keep my children healthy' (relative index = 0.93, p < 0.000). However, substantial number of parents believed that influenza is not a serious disease (18.5%) and vaccines are accompanied by several side effects (24.6%). A positive attitude was reflected among parents who were aware of influenza vaccines in Pakistan. About 35% participants believed that influenza vaccines are not required for healthy children. Current study demonstrated very low vaccination rate against influenza. Awareness and health literacy regarding influenza vaccine is poor among parents. These findings necessitate the need to appropriately structured awareness programs regarding influenza vaccination among parents.
Swietenia macrophylla King (Meliaceae) is an endangered and medicinally important plant indigenous to tropical and subtropical regions of the World. S. macrophylla has been widely used in folk medicine to treat various diseases. The review reveals that limonoids and its derivatives are the major constituents of S. macrophylla. There are several data in the literature indicating a great variety of pharmacological activities of S. macrophylla, which exhibits antimicrobial, anti-inflammatory, antioxidant effects, antimutagenic, anticancer, antitumor and antidiabetic activities. Various other activities like anti-nociceptive, hypolipidemic, antidiarrhoeal, anti-infective, antiviral, antimalarial, acaricidal, antifeedant and heavy metal phytoremediation activity have also been reported. In view of the immense medicinal importance of S. macrophylla, this review aimed at compiling all currently available information on its ethnomedicinal uses, phytochemistry and biological activities of S. macrophylla, showing its importance.
Elephantopus scaber also known as Elephant's foot (Asteraceae family) has a plethora of traditional applications including dysuria, diarrhea, dysentery, leukemia and cancer. This study aimed to investigate the apoptosis inducing effects of E. scaber and the underlying mechanisms in HCT116 colorectal cell line.
Elephantopus scaber L. (family: Asteraceae) has been traditionally utilized as a folkloric medicine and scientifically shown to exhibit anti-inflammatory activities in various in vivo inflammatory models. Given the lack of study on the effect of E. scaber in neuroinflammation, this study aimed to investigate the anti-neuroinflammatory effect and the underlying mechanisms of ethyl acetate fraction from the leaves of E. scaber (ESEAF) on the release of pro-inflammatory mediators in lipopolysaccharide (LPS)-induced microglia cells (BV-2). Present findings showed that ESEAF markedly attenuated the translocation of NF-κB to nucleus concomitantly with the significant mitigation on the LPS-induced production of NO, iNOS, COX-2, PGE2, IL-1β, and TNF-α. These inflammatory responses were reduced via the inhibition of p38. Besides, ESEAF was shown to possess antioxidant activities evident by the DPPH and SOD scavenging activities. The intracellular catalase enzyme activity was enhanced by ESEAF in the LPS-stimulated BV-2 cells. Furthermore, the formation of ROS induced by LPS in BV-2 cells was reduced upon the exposure to ESEAF. Intriguingly, the reduction of ROS was found in concerted with the activation of Nrf2 and HO-1. It is conceivable that the activation promotes the scavenging power of antioxidant enzymes as well as to ameliorate the inflammatory response in LPS-stimulated BV-2 cells. Finally, the safety profile analysis through oral administration of ESEAF at 2000 mg/kg did not result in any mortalities, adverse effects nor histopathologic abnormalities of organs in mice. Taken altogether, the cumulative findings suggested that ESEAF holds the potential to develop as nutraceutical for the intervention of neuroinflammatory disorders.
Loranthus parasiticus Merr (L. parasiticus) is a member of Loranthaceae family and is an important medicinal plant with a long history of Chinese traditional use. L. parasiticus, also known as Sang Ji Sheng (in Chinese), benalu teh (in Malay) and baso-kisei (in Japanese), is a semiparasitic plant, which is mostly distributed in the southern and southwestern regions of China. This review aims to provide a comprehensive overview of the ethnomedicinal use, phytochemistry and pharmacological activity of L. parasiticus and to highlight the needs for further investigation and greater global development of the plant's medicinal properties. To date, pharmacological studies have demonstrated significant biological activities, which support the traditional use of the plant as a neuroprotective, tranquilizing, anticancer, immunomodulatory, antiviral, diuretic and hypotensive agent. In addition, studies have identified antioxidative, antimutagenic, antiviral, antihepatotoxic and antinephrotoxic activity. The key bioactive constituents in L. parasiticus include coriaria lactone comprised of sesquiterpene lactones: coriamyrtin, tutin, corianin, and coriatin. In addition, two proanthocyanidins, namely, AC trimer and (+)-catechin, have been recently discovered as novel to L. parasiticus. L. parasiticus usefulness as a medicinal plant with current widespread traditional use warrants further research, clinical trials and product development to fully exploit its medicinal value.
The aim of this study was to investigate the cytotoxic and apoptotic effects of Nephelium ramboutan-ake (pulasan) rind in selected human cancer cell lines. The crude ethanol extract and fractions (ethyl acetate and aqueous) of N. ramboutan-ake inhibited the growth of HT-29, HCT-116, MDA-MB-231, Ca Ski cells according to MTT assays. The N. ramboutan-ake aqueous fraction (NRAF) was found to exert the greatest cytotoxic effect against HT-29 in a dose-dependent manner. Evidence of apoptotic cell death was revealed by features such as chromatin condensation, nuclear fragmentation and apoptotic body formation. The result from a TUNEL assay strongly suggested that NRAF brings about DNA fragmentation in HT-29 cells. Phosphatidylserine (PS) externalization on the outer leaflet of plasma membranes was detected with annexin V-FITC/PI binding, confirming the early stage of apoptosis. The mitochondrial permeability transition is an important step in the induction of cellular apoptosis, and the results clearly suggested that NRAF led to collapse of mitochondrial transmembrane potential in HT-29 cells. This attenuation of mitochondrial membrane potential (Δψm) was accompanied by increased production of ROS and depletion of GSH, an increase of Bax protein expression, and induced-activation of caspase-3/7 and caspase-9. These combined results suggest that NRAF induces mitochondrial-mediated apoptosis.
Phenazine-1-carboxylic acid (PCA) is the primary active component in the newly registered, commercial biopesticide Shenqinmycin and is produced during fermentation by the engineered rhizobacterium strain Pseudomonas PA1201. Both phz1 and phz2 gene clusters contribute to PCA biosynthesis. In this study, we evaluated the role of OxyR in the regulation of PCA biosynthesis in PA1201. We first showed a functional link between oxyR expression and PCA biosynthesis. Deletion of oxyR and overexpression of oxyR both increase PCA biosynthesis. The molecular mechanisms underlying OxyR regulation of PCA production were investigated using several approaches. OxyR acts divergently in phz1 and phz2. Overexpression of oxyR activated the expression of phz1 and phz1-dependent PCA production. However, overexpression of oxyR had little effect on phz2-dependent PCA biosynthesis, while deletion of oxyR promoted phz2-dependent PCA production and exerted a negative effect on phz2 expression. Further, OxyR directly bound to the phz2 promoter region. In addition, the regulation of PCA biosynthesis by OxyR was associated with quorum sensing (QS) systems. Overexpression of OxyR positively regulated pqs QS system. Finally, transcriptomic analysis and subsequent genetic analysis revealed the small RNA phrS plays a key role in OxyR-dependent PCA accumulation. Specifically, OxyR directly binds to the phrS promoter region to positively regulate phrS expression wherein PhrS regulates the PCA positive regulator MvfR in order to control PCA biosynthesis.
Extensively produced by members of the genus Streptomyces, piericidins are a large family of microbial metabolites, which consist of main skeleton of 4-pyridinol with methylated polyketide side chain. Nonetheless, these metabolites show differences in their bioactive potentials against micro-organisms, insects and tumour cells. Due to its close structural similarity with coenzyme Q, piericidins also possess an inhibitory activity against NADH dehydrogenase as well as Photosystem II. This review studied the latest research progress of piericidins, covering the chemical structure and physical properties of newly identified members, bioactivities, biosynthetic pathway with gene clusters and future prospect. With the increasing incidence of drug-resistant human pathogen strains and cancers, this review aimed to provide clues for the development of either new potential antibiotics or anti-tumour agents.
The development of novel antioxidant compounds with high efficacy and low toxicity is of utmost importance in the medicine and food industries. Moreover, with increasing concerns about the safety of synthetic components, scientists are beginning to search for natural sources of antioxidants, especially essential oils (EOs). The combination of EOs may produce a higher scavenging profile than a single oil due to better chemical diversity in the mixture. Therefore, this exploratory study aims to assess the antioxidant activity of three EOs extracted from Cymbopogon flexuosus, Carum carvi, and Acorus calamus in individual and combined forms using the augmented-simplex design methodology. The in vitro antioxidant assays were performed using DPPH and ABTS radical scavenging approaches. The results of the Chromatography Gas-Mass spectrometry (CG-MS) characterization showed that citral (29.62%) and niral (27.32%) are the main components for C. flexuosus, while D-carvone (62.09%) and D-limonene (29.58%) are the most dominant substances in C. carvi. By contrast, β-asarone (69.11%) was identified as the principal component of A. calamus (30.2%). The individual EO exhibits variable scavenging activities against ABTS and DPPH radicals. These effects were enhanced through the mixture of the three EOs. The optimal antioxidant formulation consisted of 20% C. flexuosus, 53% C. carvi, and 27% A. calamus for DPPHIC50. Whereas 17% C. flexuosus, 43% C. carvi, and 40% A. calamus is the best combination leading to the highest scavenging activity against ABTS radical. These findings suggest a new research avenue for EOs combinations to be developed as novel natural formulations useful in food and biopharmaceutical products.
Snowdrop is an iconic early spring flowering plant of the genus Galanthus (Amaryllidaceae). Galanthus species (Galanthus spp.) are economically important plants as ornaments. Galanthus spp has gained significance scientific and commercial interest due to the discovery of Galanthamine as symptomatic treatment drug for Alzhiermer disease. This review aims to discuss the bioactivities of Galanthus spp including anticholinesterase, antimicrobial, antioxidant and anticancer potential of the extracts and chemical constituents of Galanthus spp. This review highlights that Galanthus spp. as the exciting sources for drug discovery and nutraceutical development.
Coriandrum sativum (C. sativum), belonging to the Apiaceae (Umbelliferae) family, is widely recognized for its uses in culinary and traditional medicine. C. sativum contains various phytochemicals such as polyphenols, vitamins, and many phytosterols, which account for its properties including anticancer, anti-inflammatory, antidiabetic, and analgesic effects. The cardiovascular benefits of C. sativum have not been summarized before, hence this review aims to further evaluate and discuss its effectiveness in cardiovascular diseases, according to the recent literature. An electronic search for literature was carried out using the following databases: PubMed, Scopus, Google Scholar, preprint platforms, and the Cochrane Database of Systematic Reviews. Articles were gathered from the inception of the database until August 2021. Moreover, the traditional uses and phytochemistry of coriander were surveyed in the original resources and summarized. As a result, most of the studies that cover cardiovascular benefits and fulfilled the eligibility criteria were in vivo, while only a few were in vitro and clinical studies. In conclusion, C. sativum can be deemed a functional food due to its wide range of cardiovascular benefits such as antihypertensive, anti-atherogenic, antiarrhythmic, hypolipidemic as well as cardioprotective effects.
Oral Squamous Cell Carcinoma (OSCC) remains a cancer with poor prognosis and high recurrence rate. Even with multimodal treatment options available for OSCC, tumor drug resistance is still a persistent problem, leading to increased tumor invasiveness among OSCC patients. An emerging trend of thought proposes that extracellular vesicles (EVs) play a role in facilitating tumor progression and chemoresistance via signaling between tumor cells. In particular, exosomes and microvesicles are heavily implicated in this process by various studies. Where primary studies into a particular EV-mediated chemoresistance mechanism in OSCC are limited, similar studies on other cancer cell types will be used in the discussion below to provide ideas for a new line of investigation into OSCC chemoresistance. By understanding how EVs are or may be involved in OSCC chemoresistance, novel targeted therapies such as EV inhibition may be an effective alternative to current treatment options in the near future. In this review, the current understandings on OSCC drug mechanisms under the novel context of exosomes and microvesicles were reviewed, including shuttling of miRNA content, drug efflux, alteration of vesicular pH, anti-apoptotic signaling, modulation of DNA damage repair, immunomodulation, epithelial-to-mesenchymal transition and maintenance of tumor by cancer stem cells.
A Streptomyces strain, MUM256 was isolated from Tanjung Lumpur mangrove soil in Malaysia. Characterization of the strain showed that it has properties consistent with those of the members of the genus Streptomyces. In order to explore the potential bioactivities, extract of the fermented broth culture of MUM256 was prepared with organic solvent extraction method. DPPH and SOD activity were utilized to examine the antioxidant capacity and the results have revealed the potency of MUM256 in superoxide anion scavenging activity in dose-dependent manner. The cytotoxicity of MUM256 extract was determined using cell viability assay against 8 different panels of human cancer cell lines. Among all the tested cancer cells, HCT116 was the most sensitive toward the extract treatment. At the highest concentration of tested extract, the result showed 2.3-, 2.0-, and 1.8-folds higher inhibitory effect against HCT116, HT29, and Caco-2 respectively when compared to normal cell line. This result has demonstrated that MUM256 extract was selectively cytotoxic toward colon cancer cell lines. In order to determine the constituents responsible for its bioactivities, the extract was then subjected to chemical analysis using GC-MS. The analysis resulted in the identification of chemical constituents including phenolic and pyrrolopyrazine compounds which may responsible for antioxidant and anticancer activities observed. Based on the findings of this study, the presence of bioactive constituents in MUM256 extract could be a potential source for the development of antioxidative and chemopreventive agents.
Loranthus parasiticus, a Chinese folk medicine, has been widely used for the treatment of brain diseases, particularly in southwest China. Hence, the present neuroprotection model was designed to investigate its neuroprotective properties against H(2)O(2)-induced oxidative stress in NG108-15 cells. L. parasiticus aqueous fraction (LPAF), which was selected in the present study, had proved to be the most active fraction among the other tested extracts and fractions in our previous screening. The restoration of depleted intracellular glutathione (GSH), a major endogenous antioxidant, by LPAF was observed after H(2)O(2) insult. Pretreatment with LPAF substantially reduced the production of intracellular reactive oxygen species generated from H(2)O(2). Apoptotic features such as externalization of phosphatidylserine and disruption of mitochondrial membrane potential were significantly attenuated by LPAF. In addition, cell cycle analysis revealed a prominent decrease in the H(2)O(2)-induced sub-G(1) population by LPAF. Moreover, apoptotic morphological analysis by DAPI nuclear staining demonstrated that NG108-15 cells treated with H(2)O(2) exhibited apoptotic features, while such changes were greatly reduced in cells pretreated with LPAF. Taken together, these findings confirmed that LPAF exerts marked neuroprotective activity, which raises the possibility of potential therapeutic application of LPAF for managing oxidative stress-related neurological disorders and supports the traditional use of L. parasiticus in treating brain-related diseases.