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Fulltext Molecular Mechanisms of Antiviral Agents against Dengue Virus

Lee MF, Wu YS, Poh CL

Viruses, 2023 Mar 08;15(3).
PMID: 36992414 DOI: 10.3390/v15030705

Dengue is a major global health threat causing 390 million dengue infections and 25,000 deaths annually. The lack of efficacy of the licensed Dengvaxia vaccine and the absence of a clinically approved antiviral against dengue virus (DENV) drive the urgent demand for the development of novel anti-DENV therapeutics. Various antiviral agents have been developed and investigated for their anti-DENV activities. This review discusses the mechanisms of action employed by various antiviral agents against DENV. The development of host-directed antivirals targeting host receptors and direct-acting antivirals targeting DENV structural and non-structural proteins are reviewed. In addition, the development of antivirals that target different stages during post-infection such as viral replication, viral maturation, and viral assembly are reviewed. Antiviral agents designed based on these molecular mechanisms of action could lead to the discovery and development of novel anti-DENV therapeutics for the treatment of dengue infections. Evaluations of combinations of antiviral drugs with different mechanisms of action could also lead to the development of synergistic drug combinations for the treatment of dengue at any stage of the infection.
Atmospheric polycyclic aromatic hydrocarbons (PAHs) in Asia: a review from 1999 to 2004

Chang KF, Fang GC, Chen JC, Wu YS

Environ Pollut, 2006 Aug;142(3):388-96.
PMID: 16343719

Polycyclic aromatic hydrocarbons (PAHs) are present in both gaseous and particulate phases. These compounds are considered to be atmospheric contaminants and are human carcinogens. Many studies have monitored atmospheric particulate and gaseous phases of PAH in Asia over the past 5 years. This work compares and discusses different sample collection, pretreatment and analytical methods. The main PAH sources are traffic exhausts (AcPy, FL, Flu, PA, Pyr, CHR, BeP) and industrial emissions (BaP, BaA, PER, BeP, COR, CYC). PAH concentrations are highest in areas of traffic, followed by the urban sites, and lowest in rural sites. Meteorological conditions, such as temperature, wind speed and humidity, strongly affect PAH concentrations at all sampling sites. This work elucidates the characteristics, sources and distribution, and the healthy impacts of atmospheric PAH species in Asia.
Fulltext Soluble factors from stellate cells induce pancreatic cancer cell proliferation via Nrf2-activated metabolic reprogramming and ROS detoxification

Wu YS, Looi CY, Subramaniam KS, Masamune A, Chung I

Oncotarget, 2016 Jun 14;7(24):36719-36732.
PMID: 27167341 DOI: 10.18632/oncotarget.9165

Pancreatic stellate cells (PSC), a prominent stromal cell, contribute to the progression of pancreatic ductal adenocarcinoma (PDAC). We aim to investigate the mechanisms by which PSC promote cell proliferation in PDAC cell lines, BxPC-3 and AsPC-1. PSC-conditioned media (PSC-CM) induced proliferation of these cells in a dose- and time-dependent manner. Nrf2 protein was upregulated and subsequently, its transcriptional activity was increased with greater DNA binding activity and transcription of target genes. Downregulation of Nrf2 led to suppression of PSC-CM activity in BxPC-3, but not in AsPC-1 cells. However, overexpression of Nrf2 alone resulted in increased cell proliferation in both cell lines, and treatment with PSC-CM further enhanced this effect. Activation of Nrf2 pathway resulted in upregulation of metabolic genes involved in pentose phosphate pathway, glutaminolysis and glutathione biosynthesis. Downregulation and inhibition of glucose-6-phosphate-dehydrogenase with siRNA and chemical approaches reduced PSC-mediated cell proliferation. Among the cytokines present in PSC-CM, stromal-derived factor-1 alpha (SDF-1α) and interleukin-6 (IL-6) activated Nrf2 pathway to induce cell proliferation in both cells, as shown with neutralization antibodies, recombinant proteins and signaling inhibitors. Taken together, SDF-1α and IL-6 secreted from PSC induced PDAC cell proliferation via Nrf2-activated metabolic reprogramming and ROS detoxification.
Epigenetics in Metastatic Breast Cancer: Its Regulation and Implications in Diagnosis, Prognosis and Therapeutics

Wu YS, Lee ZY, Chuah LH, Mai CW, Ngai SC

Curr Cancer Drug Targets, 2019;19(2):82-100.
PMID: 29714144 DOI: 10.2174/1568009618666180430130248

Despite advances in the treatment regimen, the high incidence rate of breast cancer (BC) deaths is mostly caused by metastasis. Recently, the aberrant epigenetic modifications, which involve DNA methylation, histone modifications and microRNA (miRNA) regulations become attractive targets to treat metastatic breast cancer (MBC). In this review, the epigenetic alterations of DNA methylation, histone modifications and miRNA regulations in regulating MBC are discussed. The preclinical and clinical trials of epigenetic drugs such as the inhibitor of DNA methyltransferase (DNMTi) and the inhibitor of histone deacetylase (HDACi), as a single or combined regimen with other epigenetic drug or standard chemotherapy drug to treat MBCs are discussed. The combined regimen of epigenetic drugs or with standard chemotherapy drugs enhance the therapeutic effect against MBC. Evidences that epigenetic changes could have implications in diagnosis, prognosis and therapeutics for MBC are also presented. Several genes have been identified as potential epigenetic biomarkers for diagnosis and prognosis, as well as therapeutic targets for MBC. Endeavors in clinical trials of epigenetic drugs against MBC should be continued although limited success has been achieved. Future discovery of epigenetic drugs from natural resources would be an attractive natural treatment regimen for MBC. Further research is warranted in translating research into clinical practice with the ultimate goal of treating MBC by epigenetic therapy in the near future.
MicroRNA expression signature of methamphetamine use and addiction in the rat nucleus accumbens

Sim MS, Soga T, Pandy V, Wu YS, Parhar IS, Mohamed Z

Metab Brain Dis, 2017 Dec;32(6):1767-1783.
PMID: 28681200 DOI: 10.1007/s11011-017-0061-x

Methamphetamine (METH) is a highly addictive psycho-stimulant that induces behavioral changes due to high level of METH-induced dopamine in the brain. Nucleus accumbens (NAc) plays an important role in these changes, especially in drug addiction. However, little is known about the underlying molecular mechanisms of METH-induced addiction. The objective of this study was to establish a behavioral model of METH use and addiction using escalating doses of METH over 15 days and to determine the global miRNA expression profiling in NAc of METH-addicted rats. In the behavioral study, the experimental rats were divided into 3 groups of 9 each: a control group, a single dose METH (5 mg/kg) treatment group and a continuous 15 alternate days METH (0.25, 0.5, 1, 2, 3, 4, 5 mg/kg) treatment group. Following that, six rats in each group were randomly selected for global miRNA profiling. Addiction behavior in rats was established using Conditioned Place Preference task. The analysis of the miRNA profiling in the NAc was performed using Affymetric microarray GeneChip® System. The findings indicated that a continuous 15 alternate days METH treatment rats showed a preference for the drug-paired compartment of the CPP. However, a one-time acute treatment with 5 mg/kg METH did not show any significant difference in preference when compared with controls. Differential profiling of miRNAs indicated that 166 miRNAs were up-regulated and 4 down-regulated in the chronic METH-treatment group when compared to controls. In comparing the chronic treatment group with the acute treatment group, 52 miRNAs were shown to be up-regulated and 7 were down-regulated. MiRNAs including miR-496-3p, miR-194-5p, miR-200b-3p and miR-181a-5p, were found to be significantly associated with METH addiction. Canonical pathway analysis revealed that a high number of METH addiction-related miRNAs play important roles in the MAPK, CREB, G-Protein Couple Receptor and GnRH Signaling pathways. Our results suggest that dynamic changes occur in the expression of miRNAs following METH exposure and addiction.
What Has Come out from Phytomedicines and Herbal Edibles for the Treatment of Cancer?

Bonam SR, Wu YS, Tunki L, Chellian R, Halmuthur MSK, Muller S, et al.

ChemMedChem, 2018 09 19;13(18):1854-1872.
PMID: 29927521 DOI: 10.1002/cmdc.201800343

Several modern treatment strategies have been adopted to combat cancer with the aim of minimizing toxicity. Medicinal plant-based compounds with the potential to treat cancer have been widely studied in preclinical research and have elicited many innovations in cutting-edge clinical research. In parallel, researchers have eagerly tried to decrease the toxicity of current chemotherapeutic agents either by combining them with herbals or in using herbals alone. The aim of this article is to present an update of medicinal plants and their bioactive compounds, or mere changes in the bioactive compounds, along with herbal edibles, which display efficacy against diverse cancer cells and in anticancer therapy. It describes the basic mechanism(s) of action of phytochemicals used either alone or in combination therapy with other phytochemicals or herbal edibles. This review also highlights the remarkable synergistic effects that arise between certain herbals and chemotherapeutic agents used in oncology. The anticancer phytochemicals used in clinical research are also described; furthermore, we discuss our own experience related to semisynthetic derivatives, which are developed based on phytochemicals. Overall, this compilation is intended to facilitate research and development projects on phytopharmaceuticals for successful anticancer drug discovery.
Polymorphisms in the androgen receptor CAG repeat sequence are related to tumour stage but not to ERG or androgen receptor expression in Malaysian men with prostate cancer

Tan JSJ, Ong KC, Ong DBL, Wu YS, Razack A, Kuppusamy S, et al.

Malays J Pathol, 2019 Dec;41(3):243-251.
PMID: 31901908

INTRODUCTION: Polymorphic expression of a CAG repeat sequence in the androgen receptor (AR) gene may influence the activity of the AR and the occurrence of prostate cancer and the TMPRSS2-ERG fusion event. Furthermore, this polymorphism may be responsible for the ethnic variation observed in prostate cancer occurrence and expression of the ERG oncogene. We investigate the expression of AR and ERG in the biopsies of Malaysian men with prostate cancer and in the same patients relate this to the length of the CAG repeat sequence in their AR gene.
MATERIALS AND METHODS: From a PSA screening initiative, 161 men were shown to have elevated PSA levels in their blood and underwent prostatic tissue biopsy. DNA was extracted from the blood, and exon 1 of the AR gene amplified by PCR and sequenced. The number of CAG repeat sequences were counted and compared to the immunohistochemical expression of ERG and AR in the matched tumour biopsies.
RESULTS: Of men with elevated PSA, 89 were diagnosed with prostate cancer, and 72 with benign prostatic hyperplasia (BPH). There was no significant difference in the length of the CAG repeat in men with prostate cancer and BPH. The CAG repeat length was not associated with; age, PSA or tumour grade, though a longer CAG repeat was associated with tumour stage. ERG and AR were expressed in 36% and 86% of the cancers, respectively. There was no significant association between CAG repeat length and ERG or AR expression. However, there was a significant inverse relationship between ERG and AR expression. In addition, a significantly great proportion of Indian men had ERG positive tumours, compared to men of Malay or Chinese descent.
CONCLUSIONS: CAG repeat length is not associated with prostate cancer or expression of ERG or AR. However, ERG appears to be more common in the prostate cancers of Malaysian Indian men than in the prostate cancers of other Malaysian ethnicities and its expression in this study was inversely related to AR expression.
Paracrine IL-6 signaling mediates the effects of pancreatic stellate cells on epithelial-mesenchymal transition via Stat3/Nrf2 pathway in pancreatic cancer cells

Wu YS, Chung I, Wong WF, Masamune A, Sim MS, Looi CY

Biochim Biophys Acta Gen Subj, 2017 Feb;1861(2):296-306.
PMID: 27750041 DOI: 10.1016/j.bbagen.2016.10.006

BACKGROUND: We previously showed that pancreatic stellate cells (PSC) secreted interleukin (IL)-6 and promoted pancreatic ductal adenocarcinoma (PDAC) cell proliferation via nuclear factor erythroid 2 (Nrf2)-mediated metabolic reprogramming. Epithelial-mesenchymal transition (EMT) is a key process for the metastatic cascade. To study the mechanism of PDAC progression to metastasis, we investigated the role of PSC-secreted IL-6 in activating EMT and the involvement of Nrf2 in this process.
METHODS: Gene expression of IL-6 and IL-6Rα in PSC and PDAC cells was measured with qRT-PCR. The role of PSC-secreted IL-6, JAK/Stat3 signaling, and Nrf2 mediation on EMT-related genes expression was also examined with qRT-PCR. EMT phenotypes were assessed with morphological change, wound healing, migration, and invasion.
RESULTS: PSC expressed higher mRNA levels of IL-6 but lower IL-6Rα compared to PDAC cells. Neutralizing IL-6 in PSC secretion reduced mesenchymal-like morphology, migration and invasion capacity, and mesenchymal-like gene expression of N-cadherin, vimentin, fibronectin, collagen I, Sip1, Snail, Slug, and Twist2. Inhibition of JAK/Stat3 signaling induced by IL-6 repressed EMT and Nrf2 gene expression. Induction of Nrf2 activity by tert-butylhydroquinone (tBHQ) increased both EMT phenotypes and gene expression (N-cadherin, fibronectin, Twist2, Snail, and Slug) repressed by IL-6 neutralizing antibody. Simultaneous inhibition of Nrf2 expression with siRNA and Stat3 signaling further repressed EMT gene expression, indicating that Stat3/Nrf2 pathway mediates EMT induced by IL-6.
CONCLUSIONS: IL-6 from PSC promotes EMT in PDAC cells via Stat3/Nrf2 pathway.
GENERAL SIGNIFICANCE: Targeting Stat3/Nrf2 pathway activated by PSC-secreted IL-6 may provide a novel therapeutic option to improve the prognosis of PDAC.
Preparation of long-term cycling stable ni-rich concentration-gradient NCMA cathode materials for li-ion batteries

Jeyakumar J, Seenivasan M, Wu YS, Wu SH, Chang JK, Jose R, et al.

J Colloid Interface Sci, 2023 Jun;639:145-159.
PMID: 36804788 DOI: 10.1016/j.jcis.2023.02.064

Nickel-rich (Ni > 90 %) cathodes are regarded as one of the most attractive because of their high energy density, despite their poor stability and cycle life. To improve their performance, in this study we synthesized a double concentration-gradient layered Li[Ni0.90Co0.04Mn0.03Al0.03]O2 oxide (CG-NCMA) using a continuous co-precipitation Taylor-Couette cylindrical reactor (TCCR) with a Ni-rich-core, an Mn-rich surface, and Al on top. The concentration-gradient morphology was confirmed through cross-sectional EDX line scanning. The as-synthesized sample exhibited excellent electrochemical performance at high rates (5C/10C), as well as cyclability (91.5 % after 100 cycles and 70.3 % after 500 cycles at 1C), superior to that (83.4 % and 47.6 %) of its non-concentration-gradient counterpart (UC-NCMA). The Mn-rich surface and presence of Al helped the material stay structurally robust, even after 500 cycles, while also suppressing side reactions between the electrode and electrolyte, resulting in better overall electrochemical performance. These enhancements in performance were studied using TEM, SEM, in-situ-XRD, XPS, CV, EIS and post-mortem analyses. This synthetic method enables the highly scalable production of CG-NCMA samples with two concentration-gradient structures for practical applications in Li-ion batteries.
Molecular dynamics simulations reveal the inhibitory mechanism of Withanolide A against α-glucosidase and α-amylase

Oyewusi HA, Wu YS, Safi SZ, Wahab RA, Hatta MHM, Batumalaie K

J Biomol Struct Dyn, 2023;41(13):6203-6218.
PMID: 35904027 DOI: 10.1080/07391102.2022.2104375

Diabetes mellitus (DM) is a global chronic disease characterized by hyperglycemia and insulin resistance. The unsavory severe gastrointestinal side-effects of synthetic drugs to regulate hyperglycemia have warranted the search for alternative treatments to inhibit the carbohydrate digestive enzymes (e.g. α-amylase and α-glucosidase). Certain phytochemicals recently captured the scientific community's attention as carbohydrate digestive enzyme inhibitors due to their low toxicity and high efficacy, specifically the Withanolides-loaded extract of Withania somnifera. That said, the present study evaluated in silico the efficacy of Withanolide A in targeting both α-amylase and α-glucosidase in comparison to the synthetic drug Acarbose. Protein-ligand interactions, binding affinity, and stability were characterized using pharmacological profiling, high-end molecular docking, and molecular-dynamic simulation. Withanolide A inhibited the activity of α-glucosidase and α-amylase better, exhibiting good pharmacokinetic properties, absorption, and metabolism. Also, Withanolide A was minimally toxic, with higher bioavailability. Interestingly, Withanolide A bonded well to the active site of α-amylase and α-glucosidase, yielding the lowest binding free energy of -82.144 ± 10.671 kcal/mol and -102.1043 ± 11.231 kcal/mol compared to the Acarbose-enzyme complexes (-63.220 ± 13.283 kcal/mol and -82.148 ± 10.671 kcal/mol). Hence, the findings supported the therapeutic potential of Withanolide A as α-amylase and α-glucosidase inhibitor for DM treatment.Communicated by Ramaswamy H. Sarma.
Fulltext Nutritional and Health Benefits of the Brown Seaweed Himanthalia elongata

Ilyas Z, Ali Redha A, Wu YS, Ozeer FZ, Aluko RE

Plant Foods Hum Nutr, 2023 Jun;78(2):233-242.
PMID: 36947371 DOI: 10.1007/s11130-023-01056-8

Himanthalia elongata is a brown seaweed containing several nutritional compounds and bioactive substances including antioxidants, dietary fibre, vitamins, fatty acids, amino acids, and macro- and trace- elements. A variety of bioactive compounds including phlorotannins, flavonoids, dietary fucoxanthin, hydroxybenzoic acid, hydroxycinnamic acid, polyphenols and carotenoids are also present in this seaweed. Multiple comparative studies were carried out between different seaweed species, wherein H. elongata was determined to exhibit high antioxidant capacity, total phenolic content, fucose content and potassium concentrations compared to other species. H. elongata extracts have also shown promising anti-hyperglycaemic and neuroprotective activities. H. elongata is being studied for its potential industrial food applications. In new meat product formulations, it lowered sodium content, improved phytochemical and fiber content in beef patties, improved properties of meat gel/emulsion systems, firmer and tougher with improved water and fat binding properties. This narrative review provides a comprehensive overview of the nutritional composition, bioactive properties, and food applications of H. elongata.
Fulltext Anticancer Activities of Surfactin and Potential Application of Nanotechnology Assisted Surfactin Delivery

Wu YS, Ngai SC, Goh BH, Chan KG, Lee LH, Chuah LH

Front Pharmacol, 2017;8:761.
PMID: 29123482 DOI: 10.3389/fphar.2017.00761

Surfactin, a cyclic lipopeptide biosurfactant produced by various strains of Bacillus genus, has been shown to induce cytotoxicity against many cancer types, such as Ehrlich ascites, breast and colon cancers, leukemia and hepatoma. Surfactin treatment can inhibit cancer progression by growth inhibition, cell cycle arrest, apoptosis, and metastasis arrest. Owing to the potent effect of surfactin on cancer cells, numerous studies have recently investigated the mechanisms that underlie its anticancer activity. The amphiphilic nature of surfactin allows its easy incorporation nano-formulations, such as polymeric nanoparticles, micelles, microemulsions, liposomes, to name a few. The use of nano-formulations offers the advantage of optimizing surfactin delivery for an improved anticancer therapy. This review focuses on the current knowledge of surfactin properties and biosynthesis; anticancer activity against different cancer models and the underlying mechanisms involved; as well as the potential application of nano-formulations for optimal surfactin delivery.
Fulltext Potential of medicinal plants to ameliorate neovascularization activities in diabetes: A systematic review

Yong PH, New SY, Azzani M, Wu YS, Chia VV, Ng ZX

Endocr Regul, 2023 Jan 01;58(1):26-39.
PMID: 38345496 DOI: 10.2478/enr-2024-0004

Hyperglycemia in diabetes mediates the release of angiogenic factors, oxidative stress, hypoxia, and inflammation, which in turn stimulate angiogenesis. Excessive angiogenesis can cause diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. All of these complications are debilitating, which may lead to an increased susceptibility to lower-limb amputations due to ulcerations and infections. In addition, microvascular alterations, segmental demyelination, and endoneurial microangiopathy may cause progressive deterioration ultimately leading to kidney failure and permanent blindness. Some medicinal plants have potent anti-angiogenic, antioxidant or anti-inflammatory properties that can ameliorate angiogenesis in diabetes. The purpose of this systematic review is to demonstrate the potential of medicinal plants in ameliorating the neovascularization activities in diabetes. Manuscripts were searched from PubMed, Science Direct, and Scopus databases, and Google Scholar was used for searching additional papers. From 1862 manuscripts searched, 1854 were excluded based on inclusion and exclusion criteria and 8 were included into this systematic review, whereas the required information was extracted and summarized. All identified medicinal plants decreased the high blood glucose levels in diabetes, except the aqueous extract of Lonicerae japonicae flos (FJL) and Vasant Kusumakar Ras. They also increased the reduced body weight in diabetes, except the aqueous extract of FL and total lignans from Fructus arctii. However, methanolic extract of Tinospora cordifolia and Vasant Kusumakar Ras were not tested for their ability to affect the body weight. Besides, all medicinal plants identified in this systematic review decreased the vascular endothelial growth factor (VEGF) protein expression and vasculature activity demonstrated by histopathological examination indicating promising anti-angiogenic properties. All medicinal plants identified in this systematic review have a potential to ameliorate neovascularization activities in diabetes by targeting the mechanistic pathways related to oxidative stress, inflammation, and angiogenesis.
Cobalt nanoclusters Deposit on Nitrogen-Doped graphene Sheets as bifunctional electrocatalysts for high performance lithium - Oxygen batteries

Palani R, Wu YS, Wu SH, Chang JK, Jose R, Yang CC

J Colloid Interface Sci, 2024 Nov 12;680(Pt A):845-858.
PMID: 39546905 DOI: 10.1016/j.jcis.2024.11.066

Rechargeable lithium-oxygen (Li-O2) batteries are being considered as the next-generation energy storage systems due to their higher theoretical energy density. However, the practical application of Li-O2 batteries is hindered by slow kinetics and the formation of side products during the oxygen reduction and evolution reactions on the cathode. These reactions lead to high overpotentials during charging and discharging. To address these challenges, we propose a simple ultrasonic method for synthesizing cobalt nanoclusters embedded in nitrogen-doped graphene nanosheets (GrZnCo) derived from metal-organic frameworks (MOFs). The resulting material, due to the retention of metallic cobalt structure, exhibits better electronic conductivity. Additionally, the GrZnCo catalyst shows vigorous catalytic activity, which can improve reaction kinetics and suppress side reactions, thus lowering the charging overpotential. We have investigated the impact of different catalyst compositions (GrZnCox; x = 1, 3, 5) by varying the amounts of cobalt and zinc. The optimum catalyst, GrZnCo3, contains high cobalt-N active components, graphitic-N, pyridinic-N, pyrrolic-N, and abundant defect structures, which enhance the electrochemical performance. The defect-rich GrZnCo3 catalyst enables Li-O2 batteries to achieve a high discharge capacity of 13500 mAh·g-1 at 50 mA·g-1 and a remarkable long-term cycling performance of over 400 cycles at 100 mA·g-1 with a limited capacity of 500 mAh·g-1. This work demonstrates an effective approach to fabricate cost-effective electrocatalysts for various energy storage systems.
Fulltext Antiviral peptides against SARS-CoV-2: therapeutic targets, mechanistic antiviral activity, and efficient delivery

Essa RZ, Wu YS, Batumalaie K, Sekar M, Poh CL

Pharmacol Rep, 2022 Dec;74(6):1166-1181.
PMID: 36401119 DOI: 10.1007/s43440-022-00432-6

The global pandemic of COVID-19 is a serious public health concern. Over 625 million confirmed cases and more than 6 million deaths have been recorded worldwide. Although several vaccines and antiviral medications have been developed, their efficacy is limited by the emerging new SARS-CoV-2 strains. Peptide-based therapeutics is a fast-growing class of new drugs and have unique advantages over large proteins and small molecules. Antiviral peptides (AVPs) are short polycationic antivirals with broad-spectrum effects, which have been shown to exert both prophylactic and therapeutic actions against reported coronaviruses. The potential therapeutic targets of AVPs are located either on the virus (e.g., E-protein and S-protein) to prohibit viral binding or host cells, particularly, those present on the cell surface (e.g., ACE2 and TMPRSS2). Despite AVPs having promising antiviral effects, their efficacy is limited by low bioavailability. Thus, nanoformulation is a prerequisite for prolonged bioavailability and efficient delivery. This review aimed to present an insight into the therapeutic AVP targets on both virus and host cells by discussing their antiviral activities and associated molecular mechanisms. Besides, it described the technique for discovering and developing possible AVPs based on their targets, as well as the significance of using nanotechnology for their efficient delivery against SARS-CoV-2.
Fulltext A Comprehensive Review on Source, Types, Effects, Nanotechnology, Detection, and Therapeutic Management of Reactive Carbonyl Species Associated with Various Chronic Diseases

Fuloria S, Subramaniyan V, Karupiah S, Kumari U, Sathasivam K, Meenakshi DU, et al.

Antioxidants (Basel), 2020 Nov 02;9(11).
PMID: 33147856 DOI: 10.3390/antiox9111075

Continuous oxidation of carbohydrates, lipids, and amino acids generate extremely reactive carbonyl species (RCS). Human body comprises some important RCS namely hexanal, acrolein, 4-hydroxy-2-nonenal, methylglyoxal, malondialdehyde, isolevuglandins, and 4-oxo-2- nonenal etc. These RCS damage important cellular components including proteins, nucleic acids, and lipids, which manifests cytotoxicity, mutagenicity, multitude of adducts and crosslinks that are connected to ageing and various chronic diseases like inflammatory disease, atherosclerosis, cerebral ischemia, diabetes, cancer, neurodegenerative diseases and cardiovascular disease. The constant prevalence of RCS in living cells suggests their importance in signal transduction and gene expression. Extensive knowledge of RCS properties, metabolism and relation with metabolic diseases would assist in development of effective approach to prevent numerous chronic diseases. Treatment approaches for RCS associated diseases involve endogenous RCS metabolizers, carbonyl metabolizing enzyme inducers, and RCS scavengers. Limited bioavailability and bio efficacy of RCS sequesters suggest importance of nanoparticles and nanocarriers. Identification of RCS and screening of compounds ability to sequester RCS employ several bioassays and analytical techniques. Present review describes in-depth study of RCS sources, types, properties, identification techniques, therapeutic approaches, nanocarriers, and their role in various diseases. This study will give an idea for therapeutic development to combat the RCS associated chronic diseases.
Fulltext Chemistry, Pharmacology and Therapeutic Potential of Swertiamarin - A Promising Natural Lead for New Drug Discovery and Development

Muhamad Fadzil NS, Sekar M, Gan SH, Bonam SR, Wu YS, Vaijanathappa J, et al.

Drug Des Devel Ther, 2021;15:2721-2746.
PMID: 34188450 DOI: 10.2147/DDDT.S299753

Swertiamarin, a seco-iridoid glycoside, is mainly found in Enicostemma littorale Blume (E. littorale) and exhibits therapeutic activities for various diseases. The present study aimed to provide a review of swertiamarin in terms of its phytochemistry, physicochemical properties, biosynthesis, pharmacology and therapeutic potential. Relevant literature was collected from several scientific databases, including PubMed, ScienceDirect, Scopus and Google Scholar, between 1990 and the present. This review included the distribution of swertiamarin in medicinal plants and its isolation, characterization, physicochemical properties and possible biosynthetic pathways. A comprehensive summary of the pharmacological activities, therapeutic potential and metabolic pathways of swertiamarin was also included after careful screening and tabulation. Based on the reported evidence, swertiamarin meets all five of Lipinski's rules for drug-like properties. Thereafter, the physicochemical properties of swertiamarin were detailed and analyzed. A simple and rapid method for isolating swertiamarin from E. littorale has been described. The present review proposed that swertiamarin may be biosynthesized by the mevalonate or nonmevalonate pathways, followed by the seco-iridoid pathway. It has also been found that swertiamarin is a potent compound with diverse pharmacological activities, including hepatoprotective, analgesic, anti-inflammatory, antiarthritis, antidiabetic, antioxidant, neuroprotective and gastroprotective activities. The anticancer activity of swertiamarin against different cancer cell lines has been recently reported. The underlying mechanisms of all these pharmacological effects are diverse and seem to involve the regulation of different molecular targets, including growth factors, inflammatory cytokines, protein kinases, apoptosis-related proteins, receptors and enzymes. Swertiamarin also modulates the activity of several transcription factors, and their signaling pathways in various pathological conditions are also discussed. Moreover, we have highlighted the toxicity profile, pharmacokinetics and possible structural modifications of swertiamarin. The pharmacological activities and therapeutic potential of swertiamarin have been extensively investigated. However, more advanced studies are required including clinical trials and studies on the bioavailability, permeability and administration of safe doses to offer swertiamarin as a novel candidate for future drug development.
Fulltext Selective phytochemicals targeting pancreatic stellate cells as new anti-fibrotic agents for chronic pancreatitis and pancreatic cancer

Ramakrishnan P, Loh WM, Gopinath SCB, Bonam SR, Fareez IM, Mac Guad R, et al.

Acta Pharm Sin B, 2020 Mar;10(3):399-413.
PMID: 32140388 DOI: 10.1016/j.apsb.2019.11.008

Activated pancreatic stellate cells (PSCs) have been widely accepted as a key precursor of excessive pancreatic fibrosis, which is a crucial hallmark of chronic pancreatitis (CP) and its formidable associated disease, pancreatic cancer (PC). Hence, anti-fibrotic therapy has been identified as a novel therapeutic strategy for treating CP and PC by targeting PSCs. Most of the anti-fibrotic agents have been limited to phase I/II clinical trials involving vitamin analogs, which are abundant in medicinal plants and have proved to be promising for clinical application. The use of phytomedicines, as new anti-fibrotic agents, has been applied to a variety of complementary and alternative approaches. The aim of this review was to present a focused update on the selective new potential anti-fibrotic agents, including curcumin, resveratrol, rhein, emodin, green tea catechin derivatives, metformin, eruberin A, and ellagic acid, in combating PSC in CP and PC models. It aimed to describe the mechanism(s) of the phytochemicals used, either alone or in combination, and the associated molecular targets. Most of them were tested in PC models with similar mechanism of actions, and curcumin was tested intensively. Future research may explore the issues of bioavailability, drug design, and nano-formulation, in order to achieve successful clinical outcomes with promising activity and tolerability.
Fulltext Nanodetection of Head and Neck Cancer on Titanium Oxide Sensing Surface

Wang Y, Guo Y, Lu J, Sun Y, Yu X, Gopinath SCB, et al.

Nanoscale Res Lett, 2020 Feb 03;15(1):33.
PMID: 32016709 DOI: 10.1186/s11671-020-3262-x

Head and neck cancer is a heterogeneous disease, originating in the squamous cells lining the larynx (voice box), mouth, pharynx (throat), nasal cavity and salivary glands. Head and neck cancer diagnosis at the later stage is greatly influencing the survival rate of the patient. It makes a mandatory situation to identify this cancer at the earlier stages of development with a suitable biomarker. Squamous cell carcinoma antigen (SCC-Ag) is a circulating serum tumour biomarker, and the elevated level has been found in the head and neck cancer patients and highly correlated with the tumour volume. The present research was carried out to detect and quantify the level of SCC-Ag on titanium oxide (TiO2)-modified interdigitated electrode sensor (IDE) by SCC-Ag antibody. The detection of SCC-Ag was found at the level of 100 fM, while it was improved to 10 fM when the antibody was conjugated with gold nanostar, representing a 10-fold improvement. Interestingly, this enhancement in sensitivity is 1000-folds higher than other substrates. Moreover, the specificity analysis was carried out using two different control proteins and noticed that the antibody only recognised SCC-Ag, indicating the specific detection on IDE-TiO2 sensing surface.
Fulltext Kaempferia galanga L.: Progresses in Phytochemistry, Pharmacology, Toxicology and Ethnomedicinal Uses

Wang SY, Zhao H, Xu HT, Han XD, Wu YS, Xu FF, et al.

Front Pharmacol, 2021;12:675350.
PMID: 34737693 DOI: 10.3389/fphar.2021.675350

K. galanga is an aromatic medicinal herb. It is locally to India and distributed in China, Myanmar, Indonesia, Malaysia, and Thailand. K. galanga is a Traditional Chinese Herb Medicine (TCHM), which has been applied to treat cold, dry cough, toothaches, rheumatism, hypertension and so on. In addition, it has been used widely as spices since its highly aromas. The aim of this review is to compile and update the current progresses of ethnomedicinal uses, phytochemistry, pharmacology and toxicology of K. galanga. All the data on K. galanga were based on different classical literary works, multiple electronic databases including SciFinder, Web of Science, PubMed, etc. The results showed that ninety-seven compounds have been identified from rhizome of K. galanga, including terpenoids, phenolics, cyclic dipeptides, flavonoids, diarylheptanoids, fatty acids and esters. Modern pharmacology studies revealed that extracts or secondary metabolites of the herb possessed anti-inflammatory, anti-oxidant, anti-tumorous, anti-bacterial, and anti-angiogenesis effects, which were closely related to its abundant ethnomedicinal uses. In conclusion, although previous research works have provided various information of K. galanga, more in-depth studies are still necessary to systemically evaluate phytochemistry, pharmacological activities, toxicity and quality control of this herb.

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