Molecular Mechanisms of Antiviral Agents against Dengue Virus

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

Blackcurrants: A Nutrient-Rich Source for the Development of Functional Foods for Improved Athletic Performance

Blackcurrants are nutrient-rich fruits with a significant amount of bioactive compounds including vitamin C and polyphenols, especially anthocyanins. The high phytochemical content of blackcurrants promotes this fruit to become a valuable functional food ingredient with varying health-promoting activities targeting different consumers including athletes. Athletes experience oxidative stress during intense exercise, which can result in inflammation and reduced exercise performance. Antioxidants such as vitamin C and polyphenols can restore the regular oxidative status of the body. Blackcurrant supplementation has shown potential ergogenic activity to improve athlete performance during high-intensity training. Clinical trials have evaluated the effectiveness of blackcurrant supplementation on exercise performance, fat oxidation, blood lactate levels, muscle fatigue, and cardiac output. Due to the rich nutritional value of blackcurrants, they can be a potential candidate for the development of functional foods targeted at the improved performance of athletes. Blackcurrants can be used as ingredients to develop functional beverages and snacks for athletes as well as gluten-free products for celiac athletes.Blackcurrant is rich in bioactive compounds that can help improve athletic performance. It can be considered a potential bioactive ingredient to develop functional foods for athletes

Evaluation for antiviral potential of ficus deltoidea against dengue virus type-2

Dengue is one of the most widespread arthropod-borne viral diseases that cause negative impact globally. Presently, no effective drug is available to safeguard people against dengue. Ficus deltoidea is Malaysia›s famous traditional herb belonging to Moraceae family due to its pharmacological potential. F. deltoidea leaves (FDL) were extracted with n-hexane, ethyl acetate and methanol. Cell cytotoxicity study using MTT assay measuring the formazan absorbance was conducted to determine maximum non-toxic concentration on Vero cells. The antiviral activities of various concentrations of FDL extracts were assessed using virus reduction neutralisation tests against dengue virus type 2. The CC20 value of n-hexane, ethyl acetate and methanol FDL extracts were 2.99 ± 0.31, 22.15 ± 2.39, and 25.22 ± 0.42 µg/mL, respectively. Methanol FDL extract at maximum non-toxic concentration exerted strongest direct extracellular virucidal effect against DENV-2. In cell protection assay, ethyl acetate FDL extract achieved highest reduction in viral infectivity (98.17%), whereas n-hexane FDL extract showed strongest inhibition in DENV-2 viral replication in post-infection assay. Methanol FDL extract showed highest selectivity index value in direct virus inhibition, cell protection and post-infection assay. Conclusively, FDL extracts, especially methanol FDL showed potential antiviral activity against DENV-2, thus considered as promising anti-dengue agent

Fabrication of Tizanidine Loaded Patches Using Flaxseed Oil and Coriander Oil as a Penetration Enhancer for Transdermal Delivery

Transdermal drug delivery is important to maintain plasma drug concentrations for therapeutic efficacy. The current study reports the design, formulation, and evaluation of tizanidine transdermal patches formulated using chitosan and thiolated chitosan, ethyl cellulose (EC), polyvinylpyrrolidone (PVP), and Eudragit RL100 in different ratios. The tizanidine patches were formulated using flaxseed oil and coriander oil in the concentrations of 1% v/w, 2% v/w, 3% v/w, 4% v/w, 5% v/w, and 10% v/w. The patches were subjected to characterization of physicochemical property (thickness, weight uniformity, drug content, efficiency, percentage moisture uptake/loss), in vitro drug release and drug permeation, skin irritation, in vivo application, pharmacokinetics analysis, and stability studies. The results indicate that the interaction of thiolated chitosan with the negative charges of the skin opens the tight junctions of the skin, whereas flaxseed and coriander oils change the conformational domain of the skin. The novelty of this study is in the use of flaxseed and coriander oils as skin permeation enhancers for the formulation of tizanidine transdermal patches. The formulations follow non-Fickian drug release kinetics. The FTZNE23, FTZNE36 and FTZNE54, with 5% v/w flaxseed oil loaded formulations, exhibited higher flux through rabbit skin compared with FTZNE30, FTZNE35, FTZNE42, and FTZNE47, formulations loaded with 10% v/w coriander oil. The study concludes that flaxseed oil is a better choice for formulating tizanidine patches, offering optimal plasma concentration and therapeutic efficacy, and recommends the use of flaxseed and coriander oil based patches as a novel transdermal delivery system for tizanidine and related classes of drugs

Pharmacological Management of Tuberculosis, Challenges, and Potential Strategies

Tuberculosis (TB) is an infection caused by the pathogen Mycobacterium tuberculosis. The disease causes around 2 million deaths worldwide, and incidences of drug resistance only makes increases the number. The most vulnerable victims of TB infections are children and human immunodeficiency virus (HIV) patients. TB and HIV co-infections can be deadly in AIDS sufferers, as the immune system is not able to combat TB infections, hence worsening the infection. Common drugs to treat TB are available in the market, first-line drugs such as isoniazid and rifamycin are broad-spectrum drugs. Second-line antibiotics such as fluoroquinolones are also available. In this review, the mechanisms of action of TB drugs are briefly discussed, as wells as the respective resistant mechanisms of M. tuberculosis against these drugs. An updated treatment regime for TB management using bedaquiline, pretomanid and linezolid was also discussed, which shows 90% therapeutic efficacy against highly drug-resistant tuberculosis cases. Furthermore, novel strategies such as nanoparticle-conjugated TB drugs can improve drug delivery, TB drug efficiency while reducing side effects. However, importance on patient compliance to the treatment regime is still the most crucial part of TB management, hence initiatives can be put to improve patient awareness and education

Deciphering Synsepalum dulcificum as an arising phytotherapy agent : background, phytochemical and pharmacological properties with associated molecular mechanisms

Medicinal plants with less side effects are paramount important for humankind to cure various ailments as compared to newly developed allopathic medicines. Synsepalum dulcificum Daniell (Sapotaceae), is well known as miracle fruits due to its distinctive taste-modifying property. This review aimed to discuss its recent reported pharmacological properties and associated molecular mechanisms as a novel phytotherapy agent. In addition, background, phytochemical analysis and toxicological studies were also discussed as the foundation and added values for this review. It was discovered that S. dulcificum is endowed with various classes of phytochemicals, such as flavonoids, tannins, alkaloids and saponins. This review ravelled that S. dulcificum is a potent medicinal plant associated with antioxidant, antidiabetic, antimicrobial, anticancer, anti-hyperuricemic, hepatoprotective, anti-hyperlipidaemic, and anticonvulsant activities, with less toxicity shown. Future research may explore further the corresponding phytochemicals, associated molecular mechanisms, toxicological and pharmacokinetic profile before subjecting to clinical testing

Deciphering synsepalum dulcificum as an arising phytotherapy agent: Background, phytochemical and pharmacological properties with associated molecular mechanisms

Medicinal plants with less side effects are paramount important for humankind to cure various ailments as compared to newly developed allopathic medicines. Synsepalum dulcificum Daniell (Sapotaceae), is well known as miracle fruits due to its distinctive taste-modifying property. This review aimed to discuss its recent reported pharmacological properties and associated molecular mechanisms as a novel phytotherapy agent. In addition, background, phytochemical analysis and toxicological studies were also discussed as the foundation and added values for this review. It was discovered that S. dulcificum is endowed with various classes of phytochemicals, such as flavonoids, tannins, alkaloids and saponins. This review ravelled that S. dulcificum is a potent medicinal plant associated with antioxidant, antidiabetic, antimicrobial, anticancer, anti-hyperuricemic, hepatoprotective, anti-hyperlipidaemic, and anticonvulsant activities, with less toxicity shown. Future research may explore further the corresponding phytochemicals, associated molecular mechanisms, toxicological and pharmacokinetic profile before subjecting to clinical testing

SLC1A2 Gene Polymorphism Influences Methamphetamine-Induced Psychosis

SLC1A2 is a gene encoded for the excitatory amino acid transporter 2 which is responsible for glutamate reuptake from the synaptic cleft in the central nervous system. Recent studies have suggested that polymorphisms on glutamate transporters can affect drug dependence, leading to the development of neurological diseases and psychiatric disorders. Our study investigated the association of rs4755404 single nucleotide polymorphism (SNP) of the SLC1A2 gene with methamphetamine (METH) dependence and METH-induced psychosis and mania in a Malaysian population. The rs4755404 gene polymorphism was genotyped in METH-dependent male subjects (n = 285) and male control subjects (n = 251). The subjects consisted of the four ethnic groups in Malaysia (Malay, Chinese, Kadazan-Dusun, and Bajau). Interestingly, there was a significant association between rs4755404 polymorphism and METH-induced psychosis in the pooled METH-dependent subjects in terms of genotype frequency (p = 0.041). However, there was no significant association between rs4755404 polymorphism and METH dependence. Also, the rs455404 polymorphism was not significantly associated with METH-induced mania for both genotype frequencies and allele frequencies in the METH-dependent subjects, regardless of stratification into the different ethnicities. Our study suggests that the SLC1A2 rs4755404 gene polymorphism confers some susceptibility to METH-induced psychosis, especially for those who carry the GG homozygous genotype

SLC1A2 Gene Polymorphism Influences Methamphetamine-Induced Psychosis

SLC1A2 is a gene encoded for the excitatory amino acid transporter 2 which is responsible for glutamate reuptake from the synaptic cleft in the central nervous system. Recent studies have suggested that polymorphisms on glutamate transporters can affect drug dependence, leading to the development of neurological diseases and psychiatric disorders. Our study investigated the association of rs4755404 single nucleotide polymorphism (SNP) of the SLC1A2 gene with methamphetamine (METH) dependence and METH-induced psychosis and mania in a Malaysian population. The rs4755404 gene polymorphism was genotyped in METH-dependent male subjects (n = 285) and male control subjects (n = 251). The subjects consisted of the four ethnic groups in Malaysia (Malay, Chinese, Kadazan-Dusun, and Bajau). Interestingly, there was a significant association between rs4755404 polymorphism and METH-induced psychosis in the pooled METH-dependent subjects in terms of genotype frequency (p = 0.041). However, there was no significant association between rs4755404 polymorphism and METH dependence. Also, the rs455404 polymorphism was not significantly associated with METH-induced mania for both genotype frequencies and allele frequencies in the METH-dependent subjects, regardless of stratification into the different ethnicities. Our study suggests that the SLC1A2 rs4755404 gene polymorphism confers some susceptibility to METH-induced psychosis, especially for those who carry the GG homozygous genotype