Comparative ultrastructural hepatic alterations induced by free and liposome-encapsulated mefenamic acid

Mefenamic acid (MFA) is used as an anti-inflammatory, antinociceptive, and antipyretic agent for treatment of a wide range of pathological disorders. While the uncertainty of its safety and the poor oral bioavailability constitute the major limiting factors of its medical use, considerable efforts including liposomal encapsulation are needed to achieve maximum therapeutic advantages. The current work was conducted to investigate the ultrastructural alterations in the liver induced by free MFA and its liposomal preparation. Female Sprague-Dawley rats were treated with daily oral doses of either free MFA or MFA entrapped in Tween 80 inoculated liposomes at the concentration of 80 mg/kg for 28 days. Ultrathin sections were prepared from biopsies taken from the liver of each member of all animals under study and subjected to examination by transmission electron microscopy. The liver of rats that were exposed to liposomal MFA showed more ultrastructural alterations than the rats treated with the free drug. While both groups of rats demonstrated sinusoidal dilatation, Kupffer cell hyperplasia, mitochondrial damage, and nuclear alterations, rats treated with liposome-encapsulated MFA induced an increase in the multiple lysosomes formation, hepatocytic steatosis, and apoptotic activity than free MFA-treated rats. The ultrastructural findings of the present study indicate that the use of liposomal MFA induces more hepatic damage than the use of free MFA

A comprehensive review on Cosmos caudatus (ulam raja): pharmacology, ethnopharmacology, and phytochemistry

Cosmos caudatus or Ulam Raja in Malay originated from Latin America and transferred to Europe, Africa, and tropical Asia. It has been known for many traditional practices worldwide such as to rigidify bones and tone up blood circulation. The aim of this review is to summarize and discuss the association between phytochemical and pharmacological reports of C. caudatus and their traditional uses via ethnopharmacological approaches. Cosmos caudatus is a traditional medicinal plant used widely for culinary and therapeutic purposes. Phytochemical studies indicated the presence of Phenolic acids, flavonoids, tannins, sesquiterpene lactones, carbohydrates, minerals and vitamins in leaves while phenylpropanoids were in roots. Pharmacological data have been compiled for diverse activities for fresh leaves and extracts such as antihypertensive, antihyperlipidemic, antidiabetic, antimicrobial, antioxidant and antiosteoporotic. These activities experimented by in vitro and in vivo studies. Multiple C. caudatus constituents propose many potential actions in different fields such as neuroprotection, antidepression, and gastroprotection

Heavy metal quantification of classroom dust in school environment and its impacts on children health from Rawang (Malaysia)

This study aimed to determine bioavailable heavy metal concentrations (As, Cd, Co, Cu, Cr, Ni, Pb, Zn) and their potential sources in classroom dust collected from children’s hand palms in Rawang (Malaysia). This study also aimed to determine the association between bioavailable heavy metal concentration in classroom dust and children’s respiratory symptoms. Health risk assessment (HRA) was applied to evaluate health risks (non-carcinogenic and carcinogenic) due to heavy metals in classroom dust. The mean of bioavailable heavy metal concentrations in classroom dust found on children’s hand palms was shown in the following order: Zn (1.25E + 01 μg/g) > Cu (9.59E-01 μg/g) > Ni (5.34E-01 μg/g) > Cr (4.72E-02 μg/g) > Co (2.34E-02 μg/g) > As (1.77E-02 μg/g) > Cd (9.60E-03 μg/g) > Pb (5.00E-03 μg/g). Hierarchical cluster analysis has clustered 17 sampling locations into three clusters, whereby cluster 1 (S3, S4, S6, S15) located in residential areas and near to roads exposed to vehicle emissions, cluster 2 (S10, S12, S9, S7) located near Rawang town and cluster 3 (S13, S16, S1, S2, S8, S14, S11, S17, S5) located near industrial, residential and plantation areas. Emissions from vehicles, plantations and industrial activities were found as the main sources of heavy metals in classroom dust in Rawang. There is no association found between bioavailable heavy metal concentrations and respiratory symptoms, except for Cu (OR = 0.03). Health risks (non-carcinogenic and carcinogenic risks) indicated that there are no potential non-carcinogenic and carcinogenic risks of heavy metals in classroom dust toward children health

Antinociceptive activity of methanolic extract of Muntingia calabura leaves: further elucidation of the possible mechanisms

Background: Muntingia calabura (Elaecoparceae) is a medicinal plant traditionally used, particularly, by the Peruvian people to alleviate headache and cold, pain associated with gastric ulcers or to reduce the prostate gland swelling. Following the recent establishment of antinociceptive activity of M. calabura leaf, the present study was performed to further elucidate on the possible mechanisms of antinociception involved. Methods: The methanol extract of M. calabura (MEMC) was prepared in the doses of 100, 250 and 500 mg/kg. The role of bradykinin, protein kinase C, pottasium channels, and various opioid and non-opioid receptors in modulating the extract’s antinociceptive activity was determined using several antinociceptive assays. Results are presented as Mean ± standard error of mean (SEM). The one-way ANOVA test with Dunnett's multiple comparison was used to analyze and compare the data, with P < 0.05 as the limit of significance. Results: The MEMC, at all doses, demonstrated a significant (p < 0.05) dose-dependent antinociceptive activity in both the bradykinin- and phorbol 12-myristate 13-acetate (PMA)-induced nociception. Pretreatment of the 500 mg/kg MEMC with 10 mg/kg glibenclamide (an ATP-sensitive K+ channel inhibitor), the antagonist of μ-, δ- and κ-opioid receptors (namely 10 mg/kg β-funaltrexamine, 1 mg/kg naltrindole and 1 mg/kg nor-binaltorphimine), and the non-opioid receptor antagonists (namely 3 mg/kg caffeine (a non-selective adenosinergic receptor antagonist), 0.15 mg/kg yohimbine (an α2-noradrenergic antagonist), and 1 mg/kg pindolol (a β-adrenoceptor antagonist)) significantly (p < 0.05) reversed the MEMC antinociception. However, 10 mg/kg atropine (a non-selective cholinergic receptor antagonist), 0.15 mg/kg prazosin (an α1-noradrenergic antagonist) and 20 mg/kg haloperidol (a non-selective dopaminergic antagonist) did not affect the extract's antinociception. The phytochemicals screening revealed the presence of saponins, flavonoids, tannins and triterpenes while the HPLC analysis showed the presence of flavonoid-based compounds. Conclusions: The antinociceptive activity of MEMC involved activation of the non-selective opioid (particularly the μ-, δ- and κ-opioid) and non-opioid (particularly adenosinergic, α2-noradrenergic, and β-adrenergic) receptors, modulation of the ATP-sensitive K+ channel, and inhibition of bradikinin and protein kinase C actions. The discrepancies in MEMC antinociception could be due to the presence of various phytochemicals

Cosmos caudatus extract/fractions reduce smooth muscle cells migration and invasion in vitro: a potential benefit of suppressing atherosclerosis

Background: Cosmos caudatus Kunth is a medicinal herb used traditionally in Latin America and South East Asia to retard aging, rigidify bones and for several cardiovascular uses. Objective: Is to assess C. caudatus extract/fractions’ antioxidant and vascular smooth muscle cells (VSMC) migration and invasion inhibition capacity in vitro. Methods: Cosmos caudatus shoots were extracted by cold maceration in 50% ethanol to produce crude (CEE), and then the extract was fractionated to butanol (Bu.F), and aqueous fractions (Aq.f). Phenolics and saponins were quantified in extract and fractions by colorimetric methods and their antioxidant capacity was assayed in four different tests. Cytotoxic effect and safety level concentrations were determined for the fractions by using MTT assay. Migration and invasion inhibitory potential were measured in vitro at three different concentrations equivalent to (IC10, IC25, and IC50). Finally, invasion inhibitory index was calculated to obtain the best fraction(s) that show(s) the highest ratio of cell invasion inhibition to the total cell migration inhibition. Results: Butanol fraction yield was the lowest; nevertheless, its phytochemical contents, antioxidant activities as well as its potency were the highest. Unlike other fractions, Bu.F was strongly correlated with all antioxidant assays experimented. In addition, it has the highest inhibitory effect at IC25 against VSMCs migration and invasion that accounts for 53.93% and 59.94% respectively. Unexpectedly, Bu.F and CEE at IC10 displayed the highest invasion inhibitory index (approx. 68%). Conclusion: Butanol fraction of C. caudatus offers a potentiality for the discovery of new leads for preventing atherosclerosis

Safety assessment of natural products in Malaysia: current practices, challenges, and new strategies

The belief that natural products are inherently safe is a primary reason for consumers to choose traditional medicines and herbal supplements for health maintenance and disease prevention. Unfortunately, some natural products on the market have been found to contain toxic compounds, such as heavy metals and microbes, as well as banned ingredients such as aristolochic acids. It shows that the existing regulatory system is inadequate and highlights the importance of thorough safety evaluations. In Malaysia, the National Pharmaceutical Regulatory Agency is responsible for the regulatory control of medicinal products and cosmetics, including natural products. For registration purpose, the safety of natural products is primarily determined through the review of documents, including monographs, research articles and scientific reports. One of the main factors hampering safety evaluations of natural products is the lack of toxicological data from animal studies. However, international regulatory agencies such as the European Food Safety Authority and the United States Food and Drug Administration are beginning to accept data obtained using alternative strategies such as non-animal predictive toxicological tools. Our paper discusses the use of state-of-the-art techniques, including chemometrics, in silico modelling and omics technologies and their applications to the safety assessments of natural products

The geranyl acetophenone tHGA attenuates human bronchial smooth muscle proliferation via inhibition of AKT phosphorylation

Increased airway smooth muscle (ASM) mass is a prominent hallmark of airway remodeling in asthma. Inhaled corticosteroids and long-acting beta2-agonists remain the mainstay of asthma therapy, however are not curative and ineffective in attenuating airway remodeling. The geranyl acetophenone 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA), an in-house synthetic non-steroidal compound, attenuates airway hyperresponsiveness and remodeling in murine models of asthma. The effect of tHGA upon human ASM proliferation, migration and survival in response to growth factors was assessed and its molecular target was determined. Following serum starvation and induction with growth factors, proliferation and migration of human bronchial smooth muscle cells (hBSMCs) treated with tHGA were significantly inhibited without any significant effects upon cell survival. tHGA caused arrest of hBSMC proliferation at the G1 phase of the cell cycle with downregulation of cell cycle proteins, cyclin D1 and diminished degradation of cyclin-dependent kinase inhibitor (CKI), p27Kip1. The inhibitory effect of tHGA was demonstrated to be related to its direct inhibition of AKT phosphorylation, as well as inhibition of JNK and STAT3 signal transduction. Our findings highlight the anti-remodeling potential of this drug lead in chronic airway disease

Cytoprotective role of omentin against oxidative stress-induced vascular endothelial cells injury

Endothelial cell injury caused by reactive oxygen species (ROS) plays a critical role in the pathogenesis of cardiovascular diseases. Omentin, an adipocytokine that is abundantly expressed in visceral fat tissue, has been reported to possess anti-inflammatory and antidiabetic properties. However, endothelial protective effects of omentin against oxidative stress remain unclear. This study aimed to evaluate the protective effect of omentin against hydrogen peroxide (H2O2)-induced cell injury in human umbilical vein endothelial cells (HUVECs). Cytotoxicity and cytoprotective effects of omentin were evaluated using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptotic activity of HUVECs was detected using Annexin-V/PI and Hoechst 33258 staining methods. Antioxidant activity of omentin was evaluated by measuring both reactive oxygen species (ROS) levels and glutathione peroxidase (GPx) activity. No cytotoxicity effect was observed in HUVECs treated with omentin alone at concentrations of 150 to 450 ng/ml. MTT assay showed that omentin significantly prevented the cell death induced by H2O2 (p < 0.001). Hoechst staining and flow cytometry also revealed that omentin markedly prevented H2O2-induced apoptosis. Moreover, omentin not only significantly inhibited ROS production (p < 0.01) but also significantly (p < 0.01) increased GPx activity in HUVECs. In conclusion, our data suggest that omentin may protect HUVECs from injury induced by H2O2

A wake-up call: Covid-19 and its impact on reforming biosciences education towards resiliency and sustainability

COVID-19’s global pandemic has had a significant impact on bioscience education, which has switched to online learning. Every entity within the higher education ecosystem, whether technical, pedagogical, or social, has faced a number of challenges as a result of this. Regardless, biosciences education stakeholders have been fast to implement innovative strategies to maintain high standards and quality of biosciences online teaching and learning. This paper focuses on the biosciences education transition toward developing resiliency, as well as the technology resources and approaches that have been deployed in the current context to change biosciences education to be robust in the face of the COVID-19 upheaval. Finally, significant insights into ‘resilience sustainability’ approaches that may be employed in relation to the digitisation of biosciences education in a concerted effort to promote resiliency, adaptability and sustainability in biosciences education are presente

Acute and sub-chronic oral toxicity studies of methanol extract of Clinacanthus nutans in mice

Background: Clinacanthus nutans (C. nutans) Lindau (family Acanthaceae) is a shrub widely cultivated in the South East Asia region, including Malaysia. It has been traditionally used for treatment of various ailments including pain-mediated diseases. Various pharmacological activities of C. nutans have been reported except for its pain-relieving activity. This study was performed to evaluate the acute and sub-chronic oral toxicity of the methanol extract of Clinacanthus nutans (MECN) in male and female mice. Methods: In the acute toxicity study, a single dose of 5000 mg kg-1 of body weight MECN was administered orally, and was monitored for 14 consecutive days. In the sub-chronic toxicity study, the MECN was administered orally at doses of 50, 500, and 2500 mg kg-1 day-1 for 28 days. Results: Results showed that there were no clinical signs of toxicity, mortality and body weight changes in both acute and subchronic toxicity studies. There were no significant differences in relative organ weight, haematological parameters, and biochemical parameters; except for the creatinine level, which indicated significant (p<0.05) increase at doses of 500 and 2500 mg kg-1 day-1 for both sexes in the subchronic toxicity study. Necropsy, gross and histopathological observations, did not show any treatment-related signs of toxicity or abnormalities in both the acute and subchronic toxicity studies. Conclusion: In conclusion, the lethal oral dose (LD50) for the acute toxicity study is greater than 5000 mg kg-1 while for subchronic toxicity study; the no-observed-adverse-effect level (NOAEL) is greater than 2500 mg kg-1 day-1