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Hepatoprotective activity of viscosine is mediated by attenuation of hepatic macrophages and iNOS expression in CCl4-intoxicated rats

Ali H, Kabir N, Shah MR, Muhammad A, Ali S, Mehmood S, et al.

Toxicol Res (Camb), 2016 Nov 01;5(6):1688-1698.
PMID: 30090468 DOI: 10.1039/c6tx00165c

This study investigated the molecular mechanism(s) of the protective effects of a C-alkylated flavonoid, viscosine on an animal model of CCl4-induced hepatotoxicity. Viscosine at 20, 50 and 100 mg kg-1 was orally administered in a dose dependent manner per day for 3 days before the CCl4 (1 : 1 v/v in olive oil, 1 ml kg-1) treatment and 2 days after the treatment. Hepatoprotection was assessed in terms of reduction in serum enzyme activities (ALT, AST, and ALP) that occur after CCl4 injury, and by histopathology and immunohistochemistry. The rise in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in CCl4-intoxicated rats was markedly suppressed by viscosine in a concentration dependent manner. The decrease in the activity of hepatic antioxidant enzyme, SOD, was significantly prevented by viscosine, likewise gradually the levels of MDA and GSH were also normalized compared to silymarin. Viscosine also reduced the CCl4-induced damaged area from 2% to 0% as assessed by histopathology and prevented the mixed inflammatory infiltrate. Viscosine attenuated the inflammation in the liver around the injured central vein region by downregulating the CCl4 induced activation of hepatic CD68+ macrophages, thereby reducing their number as well. The expression of inducible nitric oxide synthase (iNOS) was more potentially suppressed by viscosine compared to the FDA approved positive control silymarin. The results of this study indicate that viscosine could be effective in protecting the liver from acute CCl4-induced injury. The hepatoprotective mechanisms of viscosine may be related to the free radical scavenging and attenuation of oxidative stress, as well as to the inhibition of inflammatory response in the liver. Here, we are proposing a novel mechanism of action of viscosine and suggesting that it may be a safe and better in vivo antioxidant.
Effects of supplementing organic- and inorganic-based selenium with vitamin E on intestinal histomorphology, caecal bacterial proliferation, and short-chain fatty acid profile in layer hens

Zainudin NN, Hemly NIM, Muhammad AI, Nayan N, Samsudin AA

Trop Anim Health Prod, 2023 Feb 20;55(2):90.
PMID: 36806991 DOI: 10.1007/s11250-023-03482-x

The effects of supplementing different dietary selenium (Se) sources on intestinal histomorphology, caecal bacterial proliferation, and caecum short-chain fatty acid in layer chickens were studied. A total of 120 of 54-week-old Lohman Brown Classic laying hens were subjected to four dietary treatments: control group with no Se supplementation (T1), 0.3 mg/kg of sodium selenite (T2), 0.3 mg/kg of selenium yeast (T3), and 0.3 mg/kg of bacterial Se (Stenotrophomonas maltophilia, ADS18) (T4). All treatments were also supplemented with 250 mg/kg of vitamin E. Results showed significantly (p < 0.05) higher villus height in different small intestine parts in hens fed with diets containing organic Se sources (T3 and T4), as compared to inorganic sources (T2) and control (T1). A greater crypt depth was observed for the T1 group, as compared to T3 and T4 groups. The total bacterial populations of Bifidobacteria spp. and Lactobacilli spp. were significantly increased (p < 0.05), and tEscherichia coli population was significantly decreased (p < 0.05) in T3 and T4 groups. No effect on the total caecal short-chain fatty acid (SCFAs) content was observed. However, there was a significant increase (21.5%) of the butyric acid content in T4 group. In conclusion, organic Se supplementation, particularly bacterial organic Se, enhances intestinal histomorphology, increases the beneficial caecal bacterial proliferation, and increases butyric acid content.
Fulltext Adansonia digitata L. Stem Bark Attenuates Epileptic Seizure, Depression, and Neurodegeneration by Mediating GABA and Glutamate in Pentylenetetrazol-Kindled Rats

Muhammad A, Hamman LL, Chiroma SM, Attah MOO, Dibal NI

J Pharmacopuncture, 2023 Dec 31;26(4):327-337.
PMID: 38162471 DOI: 10.3831/KPI.2023.26.4.327

OBJECTIVES: Epilepsy is a neurological condition characterized by repeated seizures attributable to synchronous neuronal activity in the brain. The study evaluated the effect of acetone extract of Adansonia digitata stem bark (ASBE) on seizure score, cognition, depression, and neurodegeneration as well as the level of Gamma-Aminobutyrate acid (GABA) and glutamate in Pentylenetetrazol-kindled rats.
METHODS: Thirty-five rats were assigned into five groups (n = 7). Groups 1-2 received normal saline and 35 mg/kg PTZ every other day. Groups 3-4 received 125 mg/kg and 250 mg/kg ASBE orally while group 5 received 5 mg/kg diazepam daily for twenty-six days. Group 3-5 received PTZ every other day, 30 mins after ASBE and diazepam.
RESULTS: The results showed that Pentylenetetrazol (PTZ) induces seizure, reduces mobility time in force swim test and decreases the normal cell number in the brain. It also significantly decreases (p < 0.05) catalase, superoxide dismutase and reduced glutathione activities compared to the ASBE pre-treated rats. Pre-treatment with ASBE reportedly decreases seizure activities significantly (p < 0.05) and increases mobility time in the force swim test. ASBE also significantly elevate (p < 0.05) the normal cell number in the hippocampus, temporal lobe, and dentate gyrus.
CONCLUSION: ASBE reduced seizure activity and prevented depression in PTZ-treated rats. It also prevented neurodegeneration by regulating glutamate and GABA levels in the brain as well as preventing lipid peroxidation.
Trypanosuppressive effects of Kolaviron may be associated with down regulation of Trypanothione reductase in Trypanosoma congolense infection

Timothy MR, Ibrahim YKE, Muhammad A, Chechet GD, Aimola IA, Mamman M

Trop Biomed, 2021 Mar 01;38(1):94-101.
PMID: 33797530 DOI: 10.47665/tb.38.1.016

Trypanothione reductase is a key enzyme that upholds the redox balance in hemoflagellate protozoan parasites such as T. congolense. This study aims at unraveling the potency of Kolaviron against trypanothione reductase in T. congolense infection using Chrysin as standard. The experiment was performed using three different approaches; in silico, in vitro and in vivo. Kolaviron and Chrysin were docked against trypanothione reductase, revealing binding energies (-9.3 and -9.0 kcal/mol) and Ki of 0.211μM and 0.151μM at the active site of trypanothione reductase as evident from the observed strong hydrophobic/hydrogen bond interactions. Parasitized blood was used for parasite isolation and trypanothione reductase activity assay using standard protocol. Real-time PCR (qPCR) assay was implored to monitor expression of trypanothione reductase using primers targeting the 177-bp repeat satellite DNA in T. congolense with SYBR Green to monitor product accumulation. Kolaviron showed IC50 values of 2.64μg/ml with % inhibition of 66.78 compared with Chrysin with IC50 values of 1.86μg/ml and % inhibition of 53.80. In vivo studies following the administration of these compounds orally after 7 days post inoculation resulted in % inhibition of Chrysin (57.67) and Kolaviron (46.90). Equally, Kolaviron relative to Chrysin down regulated the expression trypanothione reductase gene by 1.352 as compared to 3.530 of the infected group, in clear agreement with the earlier inhibition observed at the fine type level. Overall, the findings may have unraveled the Kolaviron potency against Trypanosoma congolense infection in rats.
Fulltext Knowledge, Awareness, and Practice of Safety and Emergency Response Among Scuba Divers in Malaysia: Questionnaire Development and Validation

Muhammad A, Wan Mohammad WMZ, Idris SRA, Ismail AF

Cureus, 2024 Feb;16(2):e53521.
PMID: 38445119 DOI: 10.7759/cureus.53521

INTRODUCTION: Safety has become paramount to ensure that scuba diving continues to expand into new markets, with minimal risks, and that scuba diving translates into a safe and relaxed adventure in response to growing market demands. Research focusing on assessing the knowledge, awareness, and practices (KAP) regarding safety and emergency response among scuba divers has been limited, and there is a need for validated assessment tools in this area.
METHODS: This study involved 555 scuba divers in Malaysia, and the questionnaire underwent a thorough development and validation process, including content and face validity assessments, as well as exploratory factor analysis. The validation of the knowledge domain was conducted using Item Response Theory (IRT) analysis, while awareness and practice were validated through exploratory and confirmatory factor analyses (EFA and CFA).
RESULTS: The content validity of the instrument was confirmed, with all items scoring over 80% for Item Content Validity Index (I-CVI), Scale Content Validity Index (S-CVI), and Scale Content Validity Index/Average (S-CVI/AVE). The initial draft comprises three domains: knowledge, awareness, and practice. Knowledge items were analyzed using IRT and demonstrated acceptable difficulty and discrimination levels. For the awareness and practice domains, EFA showed a Kaiser-Meyer-Olkin measure (KMO) of 0.83 and 0.79, respectively, with a significant Bartlett's test of Sphericity (P < 0.001). EFA yielded three factors for both awareness and practice domains with a total of 12 items for awareness and 13 items for practice, with satisfactory factor loadings (≥0.3). The final model of CFA showed good fits for both awareness and practice domains in terms of absolute, parsimonious, and comparative measures. The composite reliability of awareness was acceptable with Raykov's rho of 0.71, whereas the practice domain fell slightly below the acceptable threshold at 0.55. This was attributed to low factor loading and a limited number of items within each factor. The final questionnaire now consists of 20 items for knowledge, 10 items for awareness, and 12 items for the practice domain.
CONCLUSION: The results of this validation and reliability study indicate that the newly developed questionnaire possesses favorable psychometric properties for assessing KAP related to safety and emergency response in the scuba diving context. This research is essential for harmonizing the perspectives of crucial stakeholders within the recreational scuba diving industry.
Sentiment analysis of Indonesian tweets on COVID-19 and COVID-19 vaccinations

Kalanjati VP, Hasanatuludhhiyah N, d'Arqom A, Arsyi DH, Marchianti ACN, Muhammad A, et al.

F1000Res, 2023;12:1007.
PMID: 38605817 DOI: 10.12688/f1000research.130610.3

BACKGROUND: Sentiments and opinions regarding COVID-19 and the COVID-19 vaccination on Indonesian-language Twitter are scarcely reported in one comprehensive study, and thus were aimed at our study. We also analyzed fake news and facts, and Twitter engagement to understand people's perceptions and beliefs that determine public health literacy.
METHODS: We collected 3,489,367 tweets data from January 2020 to August 2021. We analyzed factual and fake news using the string comparison method. The difflib library was used to measure similarity. The user's engagement was analyzed by averaging the engagement metrics of tweets, retweets, favorites, replies, and posts shared with sentiments and opinions regarding COVID-19 and COVID-19 vaccination.
RESULT: Positive sentiments on COVID-19 and COVID-19 vaccination dominated, however, the negative sentiments increased during the beginning of the implementation of restrictions on community activities (PPKM). The tweets were dominated by the importance of health protocols (washing hands, keeping distance, and wearing masks). Several types of vaccines were on top of the word count in the vaccine subtopic. Acceptance of the vaccination increased during the studied period, and the fake news was overweighed by the facts. The tweets were dynamic and showed that the engaged topics were changed from the nature of COVID-19 to the vaccination and virus mutation which peaked in the early and middle terms of 2021. The public sentiment and engagement were shifted from hesitancy to anxiety towards the safety and effectiveness of the vaccines, whilst changed again into wariness on an uprising of the delta variant.
CONCLUSION: Understanding public sentiment and opinion can help policymakers to plan the best strategy to cope with the pandemic. Positive sentiments and fact-based opinions on COVID-19, and COVID-19 vaccination had been shown predominantly. However, sufficient health literacy levels could yet be predicted and sought for further study.
Effects of supplementation of different selenium sources on lipid profile, selenium, and vitamin E concentration of yolk

Hemly NIM, Zainudin NN, Muhammad AI, Loh TC, Samsudin AA

Trop Anim Health Prod, 2024 May 01;56(4):149.
PMID: 38691179 DOI: 10.1007/s11250-024-04006-x

Egg preference as a source of protein also provides beneficial fatty acids, vital for human consumption. However, rich in lipid products are prone to oxidative damage. The study aims to determine the effect of supplementing biogenic selenium (Se) from Stenotrophomonas maltophilia, ADS18 (ADS18) in laying hens' diet on yolk lipid oxidation status (MDA), beta-carotene (β-carotene) content, cholesterol, fatty acids, Se, and vitamin E (VE) level. A total of one hundred and twenty (120) laying hens of Lohmann Brown strains aged 50 weeks, weighing 1500 to 2000 g were reared individually in A-shape two-tier stainless-steel cages sized 30 cm x 50 cm x 40 cm (width, depth height). The hens were randomly allotted into four treatments with six replications in a complete randomised design for the period of 12 weeks. The basal diet contains 100 mg/kg VE. Treatment diets consist of basal diet as control, SS containing 0.3 mg/kg sodium selenite, Se-yeast containing 0.3 mg/kg selenised yeast, and VADS18 containing 0.3 mg/kg of ADS18. Forty-eight eggs were collected and freeze-dried biweekly for analysis. The results of the present study showed that hens supplemented ADS18 had significantly (P
Fulltext Regulation of Host Immune Response against Enterobacter cloacae Proteins via Computational mRNA Vaccine Design through Transcriptional Modification

Naveed M, Jabeen K, Naz R, Mughal MS, Rabaan AA, Bakhrebah MA, et al.

Microorganisms, 2022 Aug 10;10(8).
PMID: 36014038 DOI: 10.3390/microorganisms10081621

Enterobacter cloacae is mainly responsible for sepsis, urethritis, and respiratory tract infections. These bacteria may affect the transcription of the host and particularly their immune system by producing changes in their epigenetics. In the present study, four proteins of Enterobacter cloacae were used to predict the epitopes for the construction of an mRNA vaccine against Enterobacter cloacae infections. In order to generate cellular and humoral responses, various immunoinformatic-based approaches were used for developing the vaccine. The molecular docking analysis was performed for predicting the interaction among the chosen epitopes and corresponding MHC alleles. The vaccine was developed by combining epitopes (thirty-three total), which include the adjuvant Toll-like receptor-4 (TLR4). The constructed vaccine was analyzed and predicted to cover 99.2% of the global population. Additionally, in silico immunological modeling of the vaccination was also carried out. When it enters the cytoplasm of the human (host), the codon is optimized to generate the translated mRNA efficiently. Moreover, the peptide structures were analyzed and docked with TLR-3 and TLR-4. A dynamic simulation predicted the stability of the binding complex. The assumed construct was considered to be a potential candidate for a vaccine against Enterobacter cloacae infections. Hence, the proposed construct is suitable for in vitro analyses to validate its effectiveness.
Phytochemicals from Dodonaea viscosa and their antioxidant and anticholinesterase activities with structure-activity relationships

Muhammad A, Tel-Çayan G, Öztürk M, Duru ME, Nadeem S, Anis I, et al.

Pharm Biol, 2016 Sep;54(9):1649-55.
PMID: 26866457 DOI: 10.3109/13880209.2015.1113992

Context Dodonaea viscosa (L.) Jacq (Sapindaceae) has been used in traditional medicine as antimalarial, antidiabetic and antibacterial agent, but further investigations are needed. Objective This study determines the antioxidant and anticholinesterase activities of six compounds (1-6) and two crystals (1A and 3A) isolated from D. viscosa, and discusses their structure-activity relationships. Materials and methods Antioxidant activity was evaluated using six complementary tests, i.e., β-carotene-linoleic acid; DPPH(•), ABTS(•+), superoxide scavenging, CUPRAC and metal chelating assays. Anticholinesterase activity was performed using the Elman method. Results Clerodane diterpenoids (1 and 2) and phenolics (3-6) - together with three crystals (1A, 3A and 7A) - were isolated from the aerial parts of D. viscosa. Compound 3A exhibited good antioxidant activity in DPPH (IC50: 27.44 ± 1.06 μM), superoxide (28.18 ± 1.35% inhibition at 100 μM) and CUPRAC (A0.5: 35.89 ± 0.09 μM) assays. Compound 5 (IC50: 11.02 ± 0.02 μM) indicated best activity in ABTS assay, and 6 (IC50: 14.30 ± 0.18 μM) in β-carotene-linoleic acid assay. Compounds 1 and 3 were also obtained in the crystal (1A and 3A) form. Both crystals showed antioxidant activity. Furthermore, crystal 3A was more active than 3 in all activity tests. Phenol 6 possessed moderate anticholinesterase activity against acetylcholinesterase and butyrylcholinesterase enzymes (IC50 values: 158.14 ± 1.65 and 111.60 ± 1.28 μM, respectively). Discussion and conclusion This is the first report on antioxidant and anticholinesterase activities of compounds 1, 2, 5, 6, 1A and 3A, and characterisation of 7A using XRD. Furthermore, the structure-activity relationships are also discussed in detail for the first time.
Fulltext A Generalized Laser Simulator Algorithm for Mobile Robot Path Planning with Obstacle Avoidance

Muhammad A, Ali MAH, Turaev S, Abdulghafor R, Shanono IH, Alzaid Z, et al.

Sensors (Basel), 2022 Oct 25;22(21).
PMID: 36365875 DOI: 10.3390/s22218177

This paper aims to develop a new mobile robot path planning algorithm, called generalized laser simulator (GLS), for navigating autonomously mobile robots in the presence of static and dynamic obstacles. This algorithm enables a mobile robot to identify a feasible path while finding the target and avoiding obstacles while moving in complex regions. An optimal path between the start and target point is found by forming a wave of points in all directions towards the target position considering target minimum and border maximum distance principles. The algorithm will select the minimum path from the candidate points to target while avoiding obstacles. The obstacle borders are regarded as the environment's borders for static obstacle avoidance. However, once dynamic obstacles appear in front of the GLS waves, the system detects them as new dynamic obstacle borders. Several experiments were carried out to validate the effectiveness and practicality of the GLS algorithm, including path-planning experiments in the presence of obstacles in a complex dynamic environment. The findings indicate that the robot could successfully find the correct path while avoiding obstacles. The proposed method is compared to other popular methods in terms of speed and path length in both real and simulated environments. According to the results, the GLS algorithm outperformed the original laser simulator (LS) method in path and success rate. With application of the all-direction border scan, it outperforms the A-star (A*) and PRM algorithms and provides safer and shorter paths. Furthermore, the path planning approach was validated for local planning in simulation and real-world tests, in which the proposed method produced the best path compared to the original LS algorithm.
Fulltext Genetic Diversity of Plasmodium falciparum Populations in Malaria Declining Areas of Sabah, East Malaysia

Mohd Abd Razak MR, Sastu UR, Norahmad NA, Abdul-Karim A, Muhammad A, Muniandy PK, et al.

PLoS One, 2016;11(3):e0152415.
PMID: 27023787 DOI: 10.1371/journal.pone.0152415

Malaysia has a national goal to eliminate malaria by 2020. Understanding the genetic diversity of malaria parasites in residual transmission foci can provide invaluable information which may inform the intervention strategies used to reach elimination targets. This study was conducted to determine the genetic diversity level of P. falciparum isolates in malaria residual foci areas of Sabah. Malaria active case detection was conducted in Kalabakan and Kota Marudu. All individuals in the study sites were screened for malaria infection by rapid diagnostic test. Blood from P. falciparum-infected individuals were collected on filter paper prior to DNA extraction. Genotyping was performed using merozoite surface protein-1 (MSP-1), merozoite surface protein-2 (MSP-2), glutamate rich protein (GLURP) and 10 neutral microsatellite loci markers. The size of alleles, multiplicity of infection (MOI), mean number of alleles (Na), expected heterozygosity (He), linkage disequilibrium (LD) and genetic differentiation (FST) were determined. In Kalabakan, the MSP-1 and MSP-2 alleles were predominantly K1 and FC27 family types, respectively. The GLURP genotype VI (751-800 bp) was predominant. The MOI for MSP-1 and MSP-2 were 1.65 and 1.20, respectively. The Na per microsatellite locus was 1.70. The He values for MSP-1, MSP-2, GLURP and neutral microsatellites were 0.17, 0.37, 0.70 and 0.33, respectively. In Kota Marudu, the MSP-1 and MSP-2 alleles were predominantly MAD20 and 3D7 family types, respectively. The GLURP genotype IV (651-700 bp) was predominant. The MOI for both MSP-1 and MSP-2 was 1.05. The Na per microsatellite locus was 3.60. The He values for MSP-1, MSP-2, GLURP and neutral microsatellites were 0.24, 0.25, 0.69 and 0.30, respectively. A significant LD was observed in Kalabakan (0.495, p<0.01) and Kota Marudu P. falciparum populations (0.601, p<0.01). High genetic differentiation between Kalabakan and Kota Marudu P. falciparum populations was observed (FST = 0.532). The genetic data from the present study highlighted the limited diversity and contrasting genetic pattern of P. falciparum populations in the malaria declining areas of Sabah.
Fulltext Viscosine as a Potent and Safe Antipyretic Agent Evaluated by Yeast-Induced Pyrexia Model and Molecular Docking Studies

Muhammad A, Khan B, Iqbal Z, Khan AZ, Khan I, Khan K, et al.

ACS Omega, 2019 Sep 03;4(10):14188-14192.
PMID: 31508540 DOI: 10.1021/acsomega.9b01041

The antipyretic potential of viscosine, a natural product isolated from the medicinal plant Dodonaea viscosa, was investigated using yeast-induced pyrexia rat model, and its structure-activity relationship was investigated through molecular docking analyses with the target enzymes cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1). The in vivo antipyretic experiments showed a progressive dose-dependent reduction in body temperatures of the hyperthermic test animals when injected with viscosine. Comparison of docking analyses with target enzymes showed strongest bonding interactions (binding energy -17.34 kcal/mol) of viscosine with the active-site pocket of mPGES-1. These findings suggest that viscosine shows antipyretic properties by reducing the concentration of prostaglandin E2 in brain through its mPGES-1 inhibitory action and make it a potential lead compound for developing effective and safer antipyretic drugs for treating fever and related pathological conditions.
Fulltext Bioavailability of Eurycomanone in Its Pure Form and in a Standardised Eurycoma longifolia Water Extract

Ahmad N, Samiulla DS, Teh BP, Zainol M, Zolkifli NA, Muhammad A, et al.

Pharmaceutics, 2018 Jul 11;10(3).
PMID: 29997335 DOI: 10.3390/pharmaceutics10030090

Eurycoma longifolia is one of the commonly consumed herbal preparations and its major chemical compound, eurycomanone, has been described to have antimalarial, antipyretic, aphrodisiac, and cytotoxic activities. Today, the consumption of E. longifolia is popular through the incorporation of its extract in food items, most frequently in drinks such as tea and coffee. In the current study, the characterisation of the physicochemical and pharmacokinetic (PK) attributes of eurycomanone were conducted via a series of in vitro and in vivo studies in rats and mice. The solubility and chemical stability of eurycomanone under the conditions of the gastrointestinal tract environment were determined. The permeability of eurycomanone was investigated by determining its distribution coefficient in aqueous and organic environments and its permeability using the parallel artificial membrane permeability assay system and Caco-2 cultured cells. Eurycomanone's stability in plasma and its protein-binding ability were measured by using an equilibrium dialysis method. Its stability in liver microsomes across species (mice, rat, dog, monkey, and human) and rat liver hepatocytes was also investigated. Along with the PK evaluations of eurycomanone in mice and rats, the PK parameters for the Malaysian Standard (MS: 2409:201) standardised water extract of E. longifolia were also evaluated in rats. Both rodent models showed that eurycomanone in both the compound form and extract form had a half-life of 0.30 h. The differences in the bioavailability of eurycomanone in the compound form between the rats (11.8%) and mice (54.9%) suggests that the PK parameters cannot be directly extrapolated to humans. The results also suggest that eurycomanone is not readily absorbed across biological membranes. However, once absorbed, the compound is not easily metabolised (is stable), hence retaining its bioactive properties, which may be responsible for the various reported biological activities.
Fulltext Preliminary study on the expression of endothelial cell biology related genes in the liver of dengue virus infected mice treated with Carica papaya leaf juice

Mohd Abd Razak MR, Norahmad NA, Md Jelas NH, Jusoh B, Muhammad A, Mohmad Misnan N, et al.

BMC Res Notes, 2019 Apr 03;12(1):206.
PMID: 30944031 DOI: 10.1186/s13104-019-4242-z

OBJECTIVE: The purpose of this study was to profile and identify the endothelial cell biology related genes that are affected by dengue virus infection in the liver tissue of AG129 mice, with and without Carica papaya leaf juice treatment.
RESULTS: The dengue fever mouse model was established by intraperitoneal inoculation of dengue virus, New Guinea C strain at 2 × 106 PFU. Daily oral administration of 1000 mg/kg freeze-dried C. papaya leaf juice (FCPLJ) was done starting from day 1 to day 3 post infection. The RNA was extracted from liver tissues harvested on day 4 post infection. The expression levels of 84 genes related to mouse endothelial cell biology were determined by qRT-PCR technique. Dengue virus infection upregulated 15 genes and downregulated two genes in the liver of AG129 mice. The FCPLJ treatment upregulated monocyte chemoattractant protein 1 and downregulated intercellular adhesion molecule 1, integrin beta 3 and fibronectin 1 genes during dengue virus infection. The data showed the potential effect of FCPLJ treatment on the expression profile of endothelial cell biology related genes in the liver of dengue virus infected-AG129 mice. Further proteomic studies are needed to determine the functional roles of the genes affected by FCPLJ treatment.
Fulltext Suppressive Effects ofClerodendrum volubileP Beauv. [Labiatae] Methanolic Extract and Its Fractions on Type 2 Diabetes and Its Complications

Erukainure OL, Hafizur RM, Kabir N, Choudhary MI, Atolani O, Banerjee P, et al.

Front Pharmacol, 2018;9:8.
PMID: 29449808 DOI: 10.3389/fphar.2018.00008

Type 2 diabetes is the most prominent of all diabetes types, contributing to global morbidity and mortality. Availability and cost of treatment with little or no side effect especially in developing countries, remains a huge burden. This has led to the search of affordable alternative therapies especially from medicinal plants. In this study, the antidiabetic effect of the methanolic extract, dichloromethane (DCM), butanol (BuOH) and aqueous fractions ofClerodendrum volubileleaves were investigated in type 2 diabetic rats for their effect on glucose homeostasis, serum insulin level and hepatic biomarkers, lipid profile, pancreatic redox balance and Ca2+levels, and β-cell distribution and function. The DCM was further fractionated to isolate the active compounds, biochanin and 5,7,4'-trimethoxykaempferol. They were investigated for their toxicity and ADMET properties, α-glucosidase and angiotensin I converting enzyme (ACE) inhibitory activitiesin silico. There were significant (p< 0.05) decrease in blood glucose, cholesterol, LDL-C, vLDL-C, triglyceride, AST and ALT levels in all treated groups, with DCM fraction showing the best activity. All treated rats showed significantly (p< 0.05) improved anti-oxidative activities. Treatment with the DCM fraction led to significant (p< 0.05) increased serum insulin and pancreatic Ca2+levels, as well as improved β-cell distribution and function. DCM fraction also showed improved glucose tolerance. DCM fraction dose-dependently inhibited ACE activity. The toxicity class of the isolated compounds was predicted to be 5. They were also predicted to be potent inhibitors of cytochrome P (CYPs) 1A2, 2D6 and 3A4. They docked well with α-glucosidase and ACE. These results indicate the therapeutic potential of the plant against type 2 diabetes, with the DCM fraction being the most potent which may be attributed to the isolated flavones. It further suggests antihypertensive potentials of the DCM fraction. However, inhibition of CYPs by the flavones may suggest caution in usage with other prescribed drugs metabolized by these enzymes.
In vitro study on efficacy of SKF7®, a Malaysian medicinal plant product against SARS-CoV-2

Mohd Abd Razak MR, Md Jelas NH, Norahmad NA, Mohmad Misnan N, Muhammad A, Padlan N, et al.

BMC Complement Med Ther, 2024 Sep 11;24(1):333.
PMID: 39261916 DOI: 10.1186/s12906-024-04628-6

BACKGROUND: In early 2020, COVID-19 pandemic has mobilized researchers in finding new remedies including repurposing of medicinal plant products focusing on direct-acting antiviral and host-directed therapies. In this study, we performed an in vitro investigation on the standardized Marantodes pumilum extract (SKF7®) focusing on anti-SARS-CoV-2 and anti-inflammatory activities.
METHODS: Anti-SARS-CoV-2 potential of the SKF7® was evaluated in SARS-CoV-2-infected Vero E6 cells and SARS-CoV-2-infected A549 cells by cytopathic effect-based assay and RT-qPCR, respectively. Target based assays were performed on the SKF7® against the S1-ACE2 interaction and 3CL protease activities. Anti-inflammatory activity of the SKF7® was evaluated by nitric oxide inhibitory and TLR2/TLR4 receptor blocker assays.
RESULTS: The SKF7® inhibited wild-type Wuhan (EC50 of 21.99 µg/mL) and omicron (EC50 of 16.29 µg/mL) SARS-CoV-2 infections in Vero-E6 cells. The SKF7® also inhibited the wild-type SARS-CoV-2 infection in A549 cells (EC50 value of 6.31 µg/mL). The SKF7® prominently inhibited 3CL protease activity. The SKF7® inhibited the LPS induced-TLR4 response with the EC50 of 16.19 µg/mL.
CONCLUSIONS: In conclusion, our in vitro study highlighted anti-SARS-CoV-2 and anti-inflammatory potentials of the SKF7®. Future pre-clinical in vivo studies focusing on antiviral and immunomodulatory potentials of the SKF7® in affecting the COVID-19 pathogenesis are warranted.
Fulltext Health literacy on COVID-19 and COVID-19 vaccinations in Indonesia

Kalanjati VP, Hasanatuludhhiyah N, d'Arqom A, Muhammad A, Marchianti ACN, Arsyi DH, et al.

F1000Res, 2022;11:1296.
PMID: 36636472 DOI: 10.12688/f1000research.125551.2

Introduction: Health literacy on the coronavirus disease 2019 (COVID-19) affects people's capability to ascertain their health and health care quality during the pandemic. The objective of this study was to determine the levels of health literacy about COVID-19 vaccines and vaccinations (Vaccines and Vaccinations literacy-VL) in the Indonesian adult general population, assessing the perceptions of the respondents about current adult immunization and beliefs about vaccinations in general, and analyzing correlations of these variables with the VL levels. Methods: A cross-sectional study using a rapid survey was administered via the Internet. Data were analyzed using descriptive and inferential statistics; the internal consistency of the VL scales was evaluated using Cronbach's alpha coefficient; the inter-correlation between the functional and interactive-critical VL questions, the underlying components (factors) and each question's load on the components were identified using a Principal Component Analysis (PCA). An alpha level lesser than 0.05 was considered significant. Results: Responses to functional- and interactive/ critical- VL questions were acceptable and showed internal consistency (Cronbach's alpha = 0.817 and 0.699, respectively), lowest values observed were 0.806 for functional scale and 0.640 for the interactive-critical scale. The PCA demonstrated that there were two components accounting for 52.45% of the total variability. Approximately 60% of respondents were females (n=686). Almost all respondents used the internet to seek information regarding COVID-19 and COVID-19 vaccinations. Many used at least one social media actively with 74.4% of respondents sometimes believing the validity of this information. Conclusions: High scores were observed in both functional- and interactive/ critical-VL, and were quite in a balance between sexes in the prior VL and higher in females for the latter; these were also closely related to the educational level and age group. It is crucial to increase public health literacy in managing the pandemic.
Fulltext The oil palm VIRESCENS gene controls fruit colour and encodes a R2R3-MYB

Singh R, Low ET, Ooi LC, Ong-Abdullah M, Nookiah R, Ting NC, et al.

Nat Commun, 2014 Jun 30;5:4106.
PMID: 24978855 DOI: 10.1038/ncomms5106

Oil palm, a plantation crop of major economic importance in Southeast Asia, is the predominant source of edible oil worldwide. We report the identification of the virescens (VIR) gene, which controls fruit exocarp colour and is an indicator of ripeness. VIR is a R2R3-MYB transcription factor with homology to Lilium LhMYB12 and similarity to Arabidopsis production of anthocyanin pigment1 (PAP1). We identify five independent mutant alleles of VIR in over 400 accessions from sub-Saharan Africa that account for the dominant-negative virescens phenotype. Each mutation results in premature termination of the carboxy-terminal domain of VIR, resembling McClintock's C1-I allele in maize. The abundance of alleles likely reflects cultural practices, by which fruits were venerated for magical and medicinal properties. The identification of VIR will allow selection of the trait at the seed or early-nursery stage, 3-6 years before fruits are produced, greatly advancing introgression into elite breeding material.
Fulltext Oil palm genome sequence reveals divergence of interfertile species in Old and New worlds

Singh R, Ong-Abdullah M, Low ET, Manaf MA, Rosli R, Nookiah R, et al.

Nature, 2013 Aug 15;500(7462):335-9.
PMID: 23883927 DOI: 10.1038/nature12309

Oil palm is the most productive oil-bearing crop. Although it is planted on only 5% of the total world vegetable oil acreage, palm oil accounts for 33% of vegetable oil and 45% of edible oil worldwide, but increased cultivation competes with dwindling rainforest reserves. We report the 1.8-gigabase (Gb) genome sequence of the African oil palm Elaeis guineensis, the predominant source of worldwide oil production. A total of 1.535 Gb of assembled sequence and transcriptome data from 30 tissue types were used to predict at least 34,802 genes, including oil biosynthesis genes and homologues of WRINKLED1 (WRI1), and other transcriptional regulators, which are highly expressed in the kernel. We also report the draft sequence of the South American oil palm Elaeis oleifera, which has the same number of chromosomes (2n = 32) and produces fertile interspecific hybrids with E. guineensis but seems to have diverged in the New World. Segmental duplications of chromosome arms define the palaeotetraploid origin of palm trees. The oil palm sequence enables the discovery of genes for important traits as well as somaclonal epigenetic alterations that restrict the use of clones in commercial plantings, and should therefore help to achieve sustainability for biofuels and edible oils, reducing the rainforest footprint of this tropical plantation crop.
Fulltext The oil palm SHELL gene controls oil yield and encodes a homologue of SEEDSTICK

Singh R, Low ET, Ooi LC, Ong-Abdullah M, Ting NC, Nagappan J, et al.

Nature, 2013 Aug 15;500(7462):340-4.
PMID: 23883930 DOI: 10.1038/nature12356

A key event in the domestication and breeding of the oil palm Elaeis guineensis was loss of the thick coconut-like shell surrounding the kernel. Modern E. guineensis has three fruit forms, dura (thick-shelled), pisifera (shell-less) and tenera (thin-shelled), a hybrid between dura and pisifera. The pisifera palm is usually female-sterile. The tenera palm yields far more oil than dura, and is the basis for commercial palm oil production in all of southeast Asia. Here we describe the mapping and identification of the SHELL gene responsible for the different fruit forms. Using homozygosity mapping by sequencing, we found two independent mutations in the DNA-binding domain of a homologue of the MADS-box gene SEEDSTICK (STK, also known as AGAMOUS-LIKE 11), which controls ovule identity and seed development in Arabidopsis. The SHELL gene is responsible for the tenera phenotype in both cultivated and wild palms from sub-Saharan Africa, and our findings provide a genetic explanation for the single gene hybrid vigour (or heterosis) attributed to SHELL, via heterodimerization. This gene mutation explains the single most important economic trait in oil palm, and has implications for the competing interests of global edible oil production, biofuels and rainforest conservation.

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