ABSTRACT
Dengue virus (DENV2) is the cause of dengue disease and a worldwide health problem. DENV2 replicates in the host cell using polyproteins such as NS3 protease in conjugation with NS2B cofactor, making NS3 protease a promising antiviral drug-target. This study investigated the efficacy of 'Niloticin' against NS2B/NS3-protease. In silico and in vitro analyses were performed which included interaction of niloticin with NS2B/NS3-protease, protein stability and flexibility, mutation effect, betweenness centrality of residues and analysis of cytotoxicity, protein expression and WNV NS3-protease activity. Similar like acyclovir, niloticin forms strong H-bonds and hydrophobic interactions with residues LEU149, ASN152, LYS74, GLY148 and ALA164. The stability of the niloticin-NS2B/NS3-protease complex was found to be stable compared to the apo NS2B/NS3-protease in structural deviation, PCA, compactness and FEL analysis. The IC50 value of niloticin was 0.14 µM in BHK cells based on in vitro cytotoxicity analysis and showed significant activity at 2.5 µM in a concentration-dependent manner. Western blotting and qRT-PCR analyses showed that niloticin reduced DENV2 protein transcription in a dose-dependent manner. Besides, niloticin confirmed the inhibition of NS3-protease by the SensoLyte 440 WNV protease detection kit. These promising results suggest that niloticin could be an effective antiviral drug against DENV2 and other flaviviruses.
ABSTRACT
The worldwide scientific community is well aware that mosquitoes are the sole agents responsible for transmitting various dreadful diseases and critical illnesses caused by vector-borne pathogens. The primary objective of this current research was to evaluate the effectiveness of methanol extract from Tricholoma equestre mushroom in controlling the early life stages of Culex quinquefasciatus Say, Anopheles stephensi Liston, and Aedes aegypti (Linnaeus in Hasselquist) mosquitoes. The larvae, pupae and eggs of these mosquitoes were exposed to four different concentrations (62.5 to 500 ppm). After 120 h of treatment, the methanol extract of T. equestre exhibited ovicidal activity ranging from 66% to 80% against the eggs of the treated mosquitoes. It also demonstrated promising larvicidal and pupicidal activity with LC50 values of 216-300 and 230-309 ppm against the early life stages of all three mosquito species. Extensive toxicity studies revealed that the methanol extract from T. equestre had no harmful effects on non-target organisms. The suitability index (SI) or predator safety factor (PSF) indicated that the methanol extract did not harm Poecilia reticulata Peters 1859, (predatory fish), Gambusia affinis S. F. Baird & Girard 1853, dragonfly nymph and Diplonychus indicus Venkatesan & Rao 1871 (water-bug). Gas chromatography-mass spectrometry (GCMS) analysis identified key compounds, including 3-butenenitrile, 2-methyl-(25.319%); 1-butanol, 2-nitro-(18.87%) and oxalic acid, heptyl propyl ester (21.82%) which may be responsible for the observed activity. Furthermore, the formulation based on the methanol extract demonstrated similar effectiveness against all treated mosquitoes at the laboratory level and was found to be non-toxic to mosquito predators. This groundbreaking research represents the first confirmation that methanol extract from T. equestre could be effectively employed in preventing mosquito-borne diseases through mosquito population control programs.
Subject(s)
Aedes , Agaricales , Anopheles , Culex , Insecticides , Odonata , Animals , Methanol/pharmacology , Mosquito Vectors , Insecticides/pharmacology , Insecticides/chemistry , Plant Extracts/chemistry , Larva , Plant Leaves/chemistryABSTRACT
Diseases transmitted by vectors have a significant collision on society and community health, particularly in tropical and subtropical regions, where they can cause large-scale outbreaks shortly after initial transmission. The intent of this investigation was to study the plant extract derived from Sigesbeckia orientalis L. in controlling the immature stages of Anopheles, Culex and Aedes mosquitoes, while also considering its potential toxicity to ecosystems. The immature stages were exposed to different extracts (62.5-500 ppm), and the mortality of larvae and pupae, as well as ovicidal activity, were noted after 24 and 120 h of the experiment. The hexane and ethyl aceate extract of S. orientalis presented 100% ovicidal activity against the eggs of Anopheles, Aedes and Culex at 500 ppm concentration after 5 days of treatment. The hexane and ethylacetate extracts presented strong larvicidal activity with LC50 values of 215.7, 332.0, 197.4 and 212.6, 694.9 and 201.7 ppm against treated mosquitoes at 24 h, respectively. The same extract also presented promising pupicidal activity. The LC50 values of hexane extract were 219.6, 353.6, 194.2 and LC50 values of ethyl acetate were 257.6, 387.8 and 259.07 ppm against early stage pupae of three vector mosquitoes, respectively. The extracts from S. orientalis had strong inhibitory activity against growth and development of mosquitoes. SI/PSF values showed that the extracts of S. orientalis did not harm Poecilia reticulata, Diplonychus indicus (Water bug), Gambusia affinis and dragon fly nymph at tested concentrations. Furthermore, examinations of histopathology and growth disruption revealed significant damage to the midgut cells in the treated larvae. The formulations utilizing hexane and ethyl acetate extracts exhibited potent activity without posing any toxicity towards non-target organisms. This study clearly indicated that hexane and ethylacetate extracts showed promising results against treated mosquitoes. The present study documents the first report of the extracts from S. orientalis and they can be further assessed to identify compounds for application purposes.
Subject(s)
Acetates , Aedes , Anopheles , Culex , Insecticides , Animals , Hexanes/pharmacology , Sigesbeckia , Ecosystem , Insecticides/pharmacology , Insecticides/chemistry , Mosquito Vectors , LarvaABSTRACT
Mosquitoes stand out as the most perilous and impactful vectors on a global scale, transmitting a multitude of infectious diseases to both humans and other animals. The primary objective of the current research was to assess the effectiveness of EOs from Ocimum tenuiflorum L. and Ocimum americanum L. in controlling Anopheles stephensi Liston. Culex quinquefasciatus Say and Aedes aegypti L. mosquitoes. The larvae, pupae and eggs of the mosquitoes were exposed to four different concentrations (6.25-50 ppm). The tested EOs resulted in >99-100 % mortality at 120 h for the eggs of all examined mosquito species. It also showed robust larvicidal and pupicidal activity with LC50 and LC90 values of 17-39, 23-60 ppm and 46-220, and 73-412 ppm against Aedes, Culex and Anopheles mosquito species, respectively, at 24 h of treatment. The Suitability Index or Predator Safety Factor demonstrated that the EOs extracted from O. tenuiflorum L. and O. americanum L. did not cause harm to P. reticulata, D. indicus (water bug), G. affinis and nymph (dragonfly). GC-MS analysis identified the major probable constituents of the oil, including Phenol, 2-Methoxy-4-(1-Propenyl)- (28.29 %); 1-Methyl-3-(1'-Methylcyclopropyl) Cyclopentene (46.46 %); (E,E,E)-3,7,11,15-Tetramethylhexadeca-1,3,6,10,14-Pentaene (18.91 %) and 1,3-Isobenzofurandione, 3a,4,7,7a-Tetrahydro-4,7-Dimethyl (33.02 %). These constituents may play a significant role in the mosquitocidal activity of the oil. The same results were identified in the formulation prepared from the EOs. This marks the first report confirming the successful utilization of EOs derived from O. tenuiflorum L. and O. americanum L. in mosquito population control initiatives.
Subject(s)
Aedes , Anopheles , Culex , Insecticides , Ocimum , Odonata , Oils, Volatile , Animals , Humans , Oils, Volatile/pharmacology , Oils, Volatile/analysis , Ocimum/chemistry , Ocimum sanctum , Mosquito Vectors , Insecticides/analysis , Larva , Plant Extracts/chemistry , Plant Leaves/chemistryABSTRACT
In this study, the complete mitogenomes of Sympis rufibasis, Lacera noctilio, Oxyodes scrobiculata, Mocis undata, and Artena dotata were newly sequenced to bring up-to-date the database using the next-generation sequencing methods. The gene order of all sequenced mitogenomes was identical consisting of 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs), and a non-coding A+T-rich region, which were common to other Lepidopteran insects. All protein-coding genes (PCGs) initiated with a canonical ATN codon and ended with TAN or an incomplete stop codon, single T. The A+T-rich region of S. rufibasis, L. noctilio, O. scrobiculata, M. undata, and A. dotata are 406 bp, 462 bp, 372 bp, 410 bp, and 406 bp long, respectively, containing number of characteristics that are distinctive to Noctuoidea moths. We analyzed concatenated amino acid sequences of protein-coding genes not including rRNAs, using Maximum Likelihood and Bayesian Inference methods. The phylogenetic analyses indicated that the tribe relationships within Erebinae were reconstructed as (Sypnini+((Erebini 1+Poaphilini 1)+((Euclidiini+Catocalini+(Hypopyrini+Erebini 2))+((Hulodini+(Poaphilini 2+Ophiusini))))). Phylogenetic analyses supported and confirmed the monophyly of the subfamilies' relationships as follows: (Hypeninae+Lymantriinae)+((Scoliopterginae+((Calpinae+Erebinae)+((Herminiinae+Aganainae)+Arctiinae)))) within Erebidae.
ABSTRACT
Tropical Bovine Theileriosis, caused by the protozoan parasite Theileria annulata, poses a significant threat to cattle populations. Currently, Buparvaquone is the sole effective naphthoquinone drug commercially available for its treatment. In our research, we delved into the potential of naturally occurring quinones as alternative treatments. We isolated two quinones, emodin and chrysophanol, from Rheum emodi Wall, and two more, embelin and lawsone, from Embelia ribes Burm.f. and Lawsonia inermis L. respectively. We assessed the anti-Theileria efficacy of these quinones in vitro using MTT and flow cytometric assays on T. annulata-infected bovine lymphocytes. Additionally, we evaluated their safety on uninfected bovine Peripheral Blood Mononuclear Cells (PBMC) and Vero cells. Emodin emerged as a promising candidate, exhibiting an IC50 value of 4 µM, surpassing that of buparvaquone. Emodin also displayed relatively low LD50 values of 1.74 mM against uninfected PBMC and 0.87 mM against Vero cells, suggesting potential safety. Remarkably, emodin demonstrated a high cell absorption rate of 71.32%. While emodin's efficacy and bioavailability are encouraging, further research is imperative to validate its safety and effectiveness for treating Tropical Bovine Theileriosis.
ABSTRACT
The aim of the present study was to identify the active principle from Catharanthus roseus leaf using larvicidal bioassay against three mosquito species viz. Aedes aegypti, Culex quinquefasciatus, and Anopheles stephensi. Preliminary studies of the three successive extracts such as hexane, chloroform, and methanol against Ae. aegypti larvae showed that the chloroform extract was more active with LC50 and LC90 values of 40.09 ppm and 189.15 ppm respectively. Bioassay guided fractionation of the active chloroform extract resulted in the isolation of a triterpenoid (ursolic acid) as the active constituent. Three derivatives acetate, formate, and benzoate were prepared using this, and they were tested for their larvicidal activity against three mosquito species. The acetyl derivative was highly active against all the three species compared to the parent compound ursolic acid; the activities of benzoate and formate were higher than ursolic acid when tested against Cx. quinquefasciatus. This is the first report related to ursolic acid from C. roseus with mosquito larvicidal activity. The pure compound could be considered for medicinal and other pharmacological applications in future.
Subject(s)
Aedes , Anopheles , Catharanthus , Culex , Insecticides , Animals , Larva , Chloroform , Insecticides/pharmacology , Plant Extracts/pharmacology , Plant Leaves , Ursolic AcidABSTRACT
MAIN CONCLUSION: Zinc deficiency altered shoot and root growth, plant biomass, yield, and ZIP family transporter gene expression in sorghum. Zinc (Zn) deficiency affects several crop plants' growth and yield, including sorghum. We have evaluated the sorghum under various concentrations of Zn supply for phenotypic changes, Zn content, and expression of Zn-regulated, iron-regulated transporter-like proteins (ZIP) family genes. Zn deficiency reduced the shoot and root growth, plant biomass, and yield by > 50%. The length and number of lateral roots were increased by more than 50% under deficient Zn compared to sufficient Zn. Ten SbZIP family transporter genes showed dynamic expression in shoot and root tissues of sorghum under deficient and sufficient Zn. SbZIP2, 5, 6, 7, and 8 were expressed in all tissues under deficient and sufficient Zn. SbZIP2, 4, 5, 6, 7, 8, and 10 were highly induced in shoot tissues by deficient Zn. The expression level of SbZIP6, 7, 8, and 9 was higher in root tissues under deficient Zn. The phylogenetic analysis revealed that most SbZIP family proteins are closely associated with the ZmZIP family of maize. The functional residues His177 and Gly182 are fully conserved in all SbZIP family transporters, as revealed by homology modeling and multiple sequence alignment. This study may provide a foundation for improving the Zn-use efficiency of sorghum.
Subject(s)
Sorghum , Zinc , Zinc/metabolism , Sorghum/metabolism , Phylogeny , Plant Proteins/metabolism , Gene Expression Regulation, Plant , Edible Grain/metabolism , Membrane Transport Proteins/metabolism , Plant Roots/metabolismABSTRACT
We sequenced the mitogenomes of two Erebid species, namely Ischyja manlia (Cramer, 1776) and Rusicada privata (Walker, 1865) to analyse the phylogenetic relationship and to establish the taxonomic position of incertae sedis members of the family Erebidae. The two circular genomes of I. manlia and R. privata were 15,879 bp and 15,563 bp long, respectively. The gene order was identical, containing 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes, and an A + T-rich region. The nucleotide compositions of the A + T-rich region of both mitogenomes were similar: 80.65% for R. privata, and 81.09% for I. manlia. The AT skew and GC skew were slightly positive in I. manlia and negative in R. privata. In I. manlia and R. privata, except for cox1 which started with CGA and TTG codons, all the other 12 PCGs started with ATN codon. The A + T-rich regions of I. manlia and R. privata were 433 and 476 bp long, respectively, and contained common characteristics of Noctuoidea moths. At present, Ischyja is treated as Erebinae incertae sedis. However, phylogenetic analysis conducted in the present study reveals that the genus Ischyja is most likely to be a member of the subfamily Erebinae.
Subject(s)
Genome, Mitochondrial , Moths , Animals , Moths/genetics , Phylogeny , Base Sequence , RNA, Transfer/genetics , CodonABSTRACT
Alzheimer's Disease (AD) is a successive neurodegenerative disorder in the aged population. Many chemicals and phytochemicals are used to treat AD. Polyphenols which occur widely in various fruits, vegetables, beverages, and some other plant sources are gaining importance in AD treatment. Polyphenols comprise various subcategories, such as phenolic acids, lignans, tannins, stilbenes, hydroxybenzoic acid, hydroxycinnamic acid, and flavonoids. These compounds, as sole entities or in combination, can be used for treating AD because they have an abundance of antioxidants that are reported to be effective in free radical scavenging, metal ion chelating, and anti-inflammatory activities. Polyphenols of various plant origins have been studied, and these have been supported by in vitro assays and in vivo studies in rodents. These molecules protect neurons against oxidative stress and deposition of amyloid-ß (Aß) and tau proteins which play a vital role in the pathogenesis of AD. Consumption of wine and other foods rich in polyphenols has a beneficial effect on the neuronal signaling pathways, playing a vital role in shielding neuronal cells from neurodegeneration. Their ability to reduce free radicals and chelate metals are of great advantage. In this review, we highlight the various polyphenols that inhibit neuronal damage and progression of AD while also providing a cure. Some of the polyphenols covered are hesperidin, resveratrol, curcumin, catechin, kaempferol, and quercetin. The mechanisms of the actions of three polyphenols are also elaborated.
Subject(s)
Alzheimer Disease , Humans , Animals , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Polyphenols/therapeutic use , Neuroprotective Agents/therapeutic use , Amyloid beta-Peptides/metabolism , tau Proteins/metabolismABSTRACT
Mosquitoes are important vectors responsible for spreading a number of diseases affecting both humans and animals. Many diseases as dengue, chikungunya, yellow fever, malaria, filariasis and Japanese encephalitis are spread by mosquitoes. There are many reports of plant extracts and their active constituents showing anti-mosquito activities as larvicidal, pupicidal, ovicidal and adulticidal activities. Persea americana Mill. (Lauraceae), known as avocado, has been reported to show many pharmacological and antimicrobial activities. In this communication, the mosquito larvicidal activities of the three-active constituents, avocadene, avocadyne and avocadenol-A, from the methanolic extract of the unripe fruit peel are presented. The three mosquito species studied were Aedes aegypti, Culex quinquefasciatus and Anopheles stephensi. All three compounds showed the highest larvicidal activity against An. stephensi, LC50 values being 2.80ppm for avocadene, 2.33ppm for avocadyne and 2.07ppm for avocadenol-A. Avocadene showed larvicidal activity of 3.73ppm against Ae. aegypti and 5.96ppm against Cx. quinquefasciatus. The LC50 value of avocadyne was 5.35ppm against Ae. aegypti and 3.98ppm against Cx. quinquefasciatus. Similarly, avocadenol-A showed 6.56ppm against Ae. aegypti and 2.35ppm against Cx. quinquefasciatus. The active constituents were isolated by bioactivity-guided fractionation by silica gel column chromatography and RP HPLC. The compounds were identified by physical and spectroscopic data and compared with literature values already reported.
Subject(s)
Culex , Insecticides , Persea , Humans , Animals , Mosquito Vectors , Fruit , Insecticides/chemistry , Larva , Plant Extracts/chemistry , Plant Leaves/chemistryABSTRACT
In the present study, the newly sequenced mitogenomes of three Noctuoid and one Hyblaeoid (Insecta: Lepidoptera) species were annotated based on next-generation sequence data. The complete mitogenome lengths of Oraesia emarginata, Actinotia polyodon, Odontodes seranensis, and Hyblaea puera were 16,668 bp, 15,347 bp, 15,419 bp, and 15,350 bp, respectively. These mitogenomes were found to encode 37 typical mitochondrial genes (13 protein-coding, 22 transfer RNA, 2 ribosomal RNA) and a control region, similar to most Lepidoptera species. Maximum likelihood (ML) methods and Bayesian inference (BI) were used to reconstruct the phylogenetic relationships of the moths. This study showed the relationships of Noctuoid families as follows: (Notodontidae + (Erebidae + (Nolidae + (Euteliidae + Noctuidae)))). Furthermore, the species H. puera was separately clustered from the Noctuoidea member groups. Till now, the species from the superfamily Hyblaeoidea have not been discussed for their phylogenetic relationships. In this study, the complete mitochondrial genome of one species from the superfamily Hyblaeoidea was analysed.
Subject(s)
Genome, Mitochondrial , Moths , Animals , Genome, Mitochondrial/genetics , Phylogeny , Bayes Theorem , Moths/genetics , RNA, Ribosomal/genetics , RNA, Transfer/geneticsABSTRACT
The larvicidalproperty of graphene oxide (GO) and thiourea-reduced graphene oxide (T-rGO)was assessed against Culexquinquefasciatuslarvae. A simple water-soluble material synthesis method was used. The transformation of graphene into graphene oxide was accomplished in a single step. Under mild conditions, grapheneoxidewasdissolved in water to form a solution. Structure, optical, and microstructural features of the synthesized samples wereevaluatedusing a variety of analytical tools to compare the samples. Both GO and RGO, as well as GO, showed strong larvicidal potential when used against the third instar larvae of the Culexquinquefasciatus mosquito, with LC50and LC90values of 1.71 and 5.17 ppm and 1.89 and 5.00 ppm, respectively. As a result, our study showed that all of the GO and T-rGO under investigation create larvicidal compounds that could be employed to support efforts to control mosquito populations. It also offers an alternative method for producing GO and rGO on a big scale, which may be used in the future for a variety of biomedical applications.The binding efficacy of the active compounds against AChE1 was studied using Auto dock and the results were observed to be highly promising.
Subject(s)
Graphite , Animals , Graphite/chemistry , Oxides/pharmacology , Oxides/chemistry , Thiourea/pharmacology , Cell Survival , WaterABSTRACT
The current research focuses on the fabrication of water-soluble, reduced graphene oxide (rGO) employing thiourea (T) using a simple cost-effective method, and subsequently examining its anticancer characteristics. The cytotoxicity caused by graphene oxide (GO) and T-rGO is investigated in detail. Biological results reveal a concentration-dependent toxicity of GO and T-rGO in human colon cancer cells HT-29. A decrease in cell viability alongside DNA fragmentation is observed. Flow cytometry analysis confirms the cytotoxic effects. The novelty in this work is the use of raw graphite powder, and oxidants such as KMNO4, NaNO3, and 98 percent H2SO4 to produce graphene oxide by a modified Hummers method. This study demonstrates a simple and affordable procedure for utilising thiourea to fabricate a water-soluble reduced graphene oxide, which will be useful in a variety of biomedical applications.
ABSTRACT
Emerging evidence supports the notion that selenium (Se) plays a beneficial role in plant development for modern crop production and is considered an essential micronutrient and the predominant source of plants. However, the essential role of selenium in plant metabolism remains unclear. When used in moderate concentrations, selenium promotes plant physiological processes such as enhancing plant growth, increasing antioxidant capacity, reducing reactive oxygen species and lipid peroxidation and offering stress resistance by preventing ferroptosis cell death. Ferroptosis, a recently discovered mechanism of regulated cell death (RCD) with unique features such as iron-dependant accumulation of lipid peroxides, is distinctly different from other known forms of cell death. Glutathione peroxidase (GPX) activity plays a significant role in scavenging the toxic by-products of lipid peroxidation in plants. A low level of GPX activity in plants causes high oxidative stress, which leads to ferroptosis. An integrated view of ferroptosis and selenium in plants and the selenium-mediated nanofertilizers (SeNPs) have been discussed in more recent studies. For instance, selenium supplementation enhanced GPX4 expression and increased TFH cell (Follicular helper T) numbers and the gene transcriptional program, which prevent lipid peroxidase and protect cells from ferroptosis. However, though ferroptosis in plants is similar to that in animals, only few studies have focused on plant-specific ferroptosis; the research on ferroptosis in plants is still in its infancy. Understanding the implication of selenium with relevance to ferroptosis is indispensable for plant bioresource technology. In this review, we hypothesize that blocking ferroptosis cell death improves plant immunity and protects plants from abiotic and biotic stresses. We also examine how SeNPs can be the basis for emerging unconventional and advanced technologies for algae/bamboo biomass production. For instance, algae treated with SeNPs accumulate high lipid profile in algal cells that could thence be used for biodiesel production. We also suggest that further studies in the field of SeNPs are essential for the successful application of this technology for the large-scale production of plant biomass.
Subject(s)
Ferroptosis , Selenium , Animals , Antioxidants/pharmacology , Biomass , Lipid Peroxidation , Lipids , Selenium/pharmacologyABSTRACT
Embelin was isolated from the chloroform extract of Embelia ribes (Burm.f.) fruits; its derivative compounds 6-bromoembelin and vilangin were prepared, and they were evaluated for mosquitocidal activities against the third instar larvae and pupae of Aedes aegypti L. and Culex quinquefasciatus Say. (Diptera: Culicidae). The concentrations used were 0.5, 1.0, 1.5, and 2.0 ppm. Embelin recorded LC50 values of 5.79 and 5.54 ppm against the larvae of Ae. aegypti and Cx. quinquefasciatus, respectively. Similarly, the LC50 values of embelin were 10.23 and 6.93 ppm against the pupae of Ae. aegypti and Cx. quinquefasciatus, respectively. Of the two derivatives tested, vilangin showed the highest larvicidal activity with LC50 values of 1.38 and 1.28 ppm against the larvae of Ae. aegypti and Cx. quinquefasciatus, respectively. Similarly, the LC50 values of vilangin were 1.60 and 1.43 ppm against the pupae of Ae. aegypti and Cx. quinquefasciatus, respectively. The LC50 values of 6-bromoembelin were 3.30 and 2.83 ppm against the larvae and 4.40 and 4.30 ppm against the pupae of Ae. aegypti and Cx. quinquefasciatus, respectively. The histopathological results displayed significant damage on cuboidal cells of the midgut (CU) in vilangin treated larvae of Ae. aegypti and Cx. quinquefasciatus at a concentration of 2.0 ppm. Similarly, peritrophic membrane (PM) was completely impaired in vilangin-treated larvae of Cx. quinquefasciatus and midgut content (MC) was very low in vilangin-treated larvae of Cx. quinquefasciatus. In addition, molecular docking and molecular dynamics studies demonstrated the efficacy of vilangin on the inhibition of acetylcholinesterase (AChE1) in Ae. aegypti and Cx. quinquefasciatus. The present results suggest that vilangin could be used to develop a natural active product against mosquito larvae.
Subject(s)
Aedes , Culex , Acetylcholinesterase , Animals , Benzoquinones , Larva , Molecular Docking Simulation , Plant Extracts/pharmacologyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants have been used by the people of developing countries to treat various diseases. WHO also recommends the use of medicines from plants source. In that, diabetes also one of the diseases that have been treated traditionally by several people all over the world. In India, Toddalia asiatica (L.) Lam. (Rutaceae) is also a medicinal plant used traditionally for the treatment of diabetes in Ayurveda. Moreover, T. asiatica is also used in a polyherbal formulation to treat diabetes. AIM OF THE STUDY: This study examined the antidiabetic with antilipidemic and antioxidant effects of flindersine isolated from T. asiatica leaves. MATERIALS AND METHODS: Diabetes was induced in Wistar rats by feeding a high-fat diet (HFD) for 15 days and injecting a single dose of 40 mg/kg b. wt. of Streptozotocin (STZ). Five days post-injection, the grouped diabetic rats were treated with 20 and 40 mg/kg of flindersine. RESULTS: Flindersine resulted in a clear decline of blood glucose levels during 28 days of treatment in two different doses. Flindersine also significantly (P ≤ 0.05; P ≤ 0.005) reduced the body weight gain, plasma insulin concentration, urea, creatinine, total cholesterol (TC), triglycerides (TG) and free fatty acids (FFA) levels and significantly increased (P ≤ 0.05; P ≤ 0.005) the total protein level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities compared to the standard drug, pioglitazone. Additionally, flindersine restored the glucose transporter protein 4 (GLUT4), adenosine monophosphate protein kinase (AMPK) and peroxisome proliferator-activated receptor γ (PPARγ) expressions in adipose tissues and skeletal muscles. CONCLUSION: It has been found that flindersine has potent antilipidemic and antidiabetic activities by improving insulin sensitivity by enhancing the phosphorylation of AMPK, GLUT4 translocation, and PPARγ agonism on adipose tissue and skeletal muscles of diabetic rats.
Subject(s)
Diabetes Mellitus, Type 2/chemically induced , Diabetes Mellitus, Type 2/drug therapy , Glucose Transporter Type 4/metabolism , Heterocyclic Compounds, 3-Ring/pharmacology , Hypoglycemic Agents/pharmacology , PPAR gamma/agonists , Animals , Antioxidants/chemistry , Antioxidants/pharmacology , Blood Glucose/drug effects , Catalase , Diabetes Mellitus, Experimental , Diet, High-Fat/adverse effects , Dose-Response Relationship, Drug , Gene Expression Regulation/drug effects , Glucose/metabolism , Glucose Transporter Type 4/genetics , Glutathione Peroxidase , Heterocyclic Compounds, 3-Ring/administration & dosage , Heterocyclic Compounds, 3-Ring/chemistry , Hypoglycemic Agents/chemistry , Hypolipidemic Agents/chemistry , Hypolipidemic Agents/pharmacology , Male , Molecular Structure , PPAR gamma/genetics , PPAR gamma/metabolism , Phytotherapy , Plant Extracts/chemistry , Plant Extracts/pharmacology , Rats , Rats, Wistar , Rutaceae/chemistry , Superoxide DismutaseABSTRACT
Vector-borne diseases such as filariasis and dengue that contribute significantly to disease burden, death, poverty, and social frailty are still a major public healthcare problem worldwide. Currently, synthetic chemicals have been used in mosquito control programs. However, repeated use of chemical insecticides causes environmental pollution and harmful effects on non-target organisms. Therefore, alternative ecofriendly sources from biological source are urgently needed to manage mosquitoes. In this respect, the present study was aimed to evaluate mosquito larvicidal and pupicidal activities of 22 crude extracts of soil actinomycetes on Culex quinquefasciatus and Aedes aegypti and to identify the active molecule. Briefly, the crude ethyl acetate extract and fractions were tested at 62.5, 125, 250, and 500 ppm and 2.5, 5.0, 7.5, and 10.0 ppm concentrations on larval and pupal stages of Cx. quinquefasciatus and Ae. aegypti. The larval and pupal mortality was assessed after 24 h of treatment. Among the 22 isolates screened, Nonomuraea sp. VAS-16 exhibited significant larvicidal and pupicidal activities against the tested mosquito species. Among the 18 fractions screened, fraction-6 showed strong larvicidal and pupicidal activities with the LC50 and LC90 values of 9.1, 18.7, 9.82, and 22.85 ppm against the larvae and LC50 and LC90 values of 10.5, 23.1, 12.3, and 24.13 ppm against the pupae of Cx. quinquefasciatus and Ae. aegypti, respectively. Fascinatingly, the isolated compound 1,2-benzenedicarboxylic acid from fraction-6 at 0.5, 1.0, 1.5, and 2.0 ppm concentration recorded lower LC50 and LC90 values of 4.27, 14.90, 4.67, and 11.90 ppm against the larvae and LC50 and LC90 values of 4.58, 12.06, 5.36, and 13.07 ppm against the pupae of Cx. quinquefasciatus and Ae. aegypti, respectively. On the other hand, the compound recorded less ovicidal activity of 11.0% and 10.3% at 2 ppm against the eggs of Cx. quinquefasciatus and Ae. aegypti, respectively. The present study clearly shows that the crude extract and the compound from Nonomuraea sp. VAS-16 can be used as an effective biopesticide in integrated mosquito management program.
Subject(s)
Actinobacteria , Aedes , Anopheles , Culex , Insecticides , Actinomyces , Animals , Biological Control Agents/analysis , Biological Control Agents/pharmacology , Insecticides/chemistry , Larva , Mosquito Vectors , Plant Extracts/chemistry , Plant Leaves/chemistry , SoilABSTRACT
A novel acute viral pneumonia induced by SARS-CoV-2 exploded at the end of 2019, causing a severe medical and economic crisis. For developing specific pharmacotherapy against SARS-CoV-2, an in silico virtual screening was developed for the available in-house molecules. The conserved domain analysis was performed to identify the highly conserved and exposed amino acid regions in the SARS-CoV-2-S RBD sites. The Protein-Protein interaction analyses demonstrated the higher affinity between the SARS-CoV-2-S and ACE2 due to varieties of significant interactions between them. The computational alanine scanning mutation study has recognized the highly stabilized amino acids in the SARS-CoV-2-S RBD/ACE2 complex. The cumulative sequence investigations have inferred that Lys417, Phe486, Asn487, Tyr489, and Gln493 are perhaps the iconic target amino acids to develop a drug molecule or vaccine against SARS-CoV-2 infection. Most of the selected compounds include luteolin, zhebeirine, 3-dehydroverticine, embelin, andrographolide, ophiopogonin D, crocin-1, sprengerinin A, B, C, peimine, etc. were exhibited distinguish drug actions through the strong hydrogen bonding with the hot spots of the RBD. Besides, the 100 ns molecular dynamics simulation and free energy binding analysis showed the significant efficacy of luteolin to inhibit the infection of SARS-CoV-2. Highlights:Highly conserved and exposed amino acids in the SARS-CoV-2-S-RBD sites has been identifiedComputational alanine scanning mutation study has recognized the highly stabilized hot spots in the SARS-CoV-2-S RBD/ACE2 complex.Virtual screening has been executed to identify the drug actions in the RBD regionMost of the selected natural products were involved in the distinctive strong interactions with hot spots of RBD to inhibit the infection of SARS-CoV-2.[Formula: see text] Communicated by Ramaswamy H. Sarma.
Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19 Drug Treatment , SARS-CoV-2 , Alanine , Amino Acids/metabolism , Binding Sites , COVID-19 Vaccines , Humans , Luteolin , Peptidyl-Dipeptidase A/chemistry , Protein Binding , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolismABSTRACT
The single nucleotide polymorphisms (SNPs) are the common genetic variations in human genomes and act as markers for molecular susceptibility of complex traits and diseases in humans. Amino acid variations in the non-synonymous SNPs (nsSNPs) in coding and non-coding regions affect the function/structure of the proteins. The Peroxisome proliferator-activated receptor gamma (PPARγ or PPARG) is a nuclear receptor that plays a significant role in lipid metabolism and insulin production and is associated with diabetes, obesity, and cancer. In this study, the PPARG sequence was retrieved from the NCBI database (dbSNP: NP_619726.2), and an analysis was done to predict the damaged/harmful mutated amino acids. We identified five mutated variants (C162S, R166W, Q286P, or Q314P and P467L), which were mostly expressed in cancer tissues and associated with insulin resistance and partial lipodystrophy. The identified mutations were induced, and the analysis of molecular dynamics simulation was established to determine the dynamic stability/flexibility of PPARG. The dynamic trajectories were analyzed by RMSD, RMSF, and Radius of Gyration (Rg) analysis; a vast difference was noticed in each of the protein structure when compared with the PPARG wild-type, and the mutations in PPARG impaired its functions, leading to more significant problems in humans.Communicated by Ramaswamy H. Sarma.