The present study was designed to investigate antioxidant, antimicrobial and cytotoxic effects of petroleum ether, chloroform and hydromethanol fraction of methanol extract of Citrus aurantifolia peel. Preliminary phytochemical screening of the fractions was done following the standard procedure. Antioxidant activity was measured using DPPH free radical scavenging assay besides measuring total phenolic and flavonoid content using Folin-Ciocalteu reagent and aluminum trichloride method, respectively. The antimicrobial activity was conducted by disc diffusion method and cytotoxic activity was determined by brine shrimp lethality bioassay. The results of phytochemical screening were indicative of the presence of steroids, alkaloids, saponins, glycosides, flavonoids in the fractions. A dose dependent scavenging activity was observed in DPPH radical scavenging assay where chloroform fraction demonstrated the highest activity with IC50 value of 153.68 ± 3.60 μg/ml. The highest phenolic content was observed in chloroform fraction (308.0 ± 6.55 mg/g gallic acid equivalent) and highest flavonoid content was found in hydromethanol fraction (132.66 ± 2.36 mg/g quercetin equivalent). The chloroform fraction showed excellent antibacterial activity against all the tested bacteria where highest zone of inhibition (19 mm) was produced against Bacillus cereus. In brine shrimp lethality bioassay, LC50 values for petroleum ether, chloroform and hydromethanol fractions were 367.39 μg/ml, 228.14 μg/ml and 296.52 μg/ml, respectively. The present findings suggested that C. aurantifolia peel could be a potent source of medicinally important secondary metabolites and further investigations can be done to identify those active compounds responsible for such bioactivity. Dhaka Univ. J. Pharm. Sci. 19(2): 161-168, 2020 (December)

Small interference RNA (siRNA) is a double-stranded RNA of 21~25 nucleotides. siRNA functions using a natural phenomenon known as RNA interference (RNAi), a gene silencing mechanism. Hypothetically, siRNA can target and regulate the expression of any disease-related gene in a sequence-specific manner. In 1993, this mechanism was noticed in a nematode Caenorhabditis elegans, later discovered in humans. After two decades, in 2018, the first siRNA therapeutics (Patisiran) were developed successfully and got approval from USFDA. Followed by three more siRNA drugs (Givosiran, Lumasiran, and Inclisiran) approved in consecutive years to treat rare, inherited genetic disorders. Recently approved one is Vutisiran with a similar indication of patisiran. Limitation of conventional therapies, this new & standard pharmacotherapy opens a new era of changing the treatment options of human diseases. Six siRNA candidates are in phase III clinical trials and are hoped to enter the pharmaceutical market soon. Challenges faced during the development of these novel therapies were off-target effects, target-specific delivery, cellular uptake, recognition by the innate immune system, limited efficacy, and others. However, chemical modification of the siRNA nucleotides in sugar, base, and phosphate moiety makes it successful in overcoming obstacles. In addition, a non-viral delivery carrier also helped in many aspects during formulation. This study is a narrative review and will summarize pharmacokinetic, pharmacodynamic, design approaches, and other attributes faced during the development of marketed siRNA products.

The induction of enzymes is a defensive mechanism for some xenobiotics, but it may alter the drug's safety and efficacy by altering the activity of metabolic enzymes. One of the major families of enzymes involved in phase I metabolism is Cytochrome P450 (CYP) enzymes which may get induced by certain drugs. Concomitant administration of drugs due to chronic disease or polypharmacy, inducers among them may cause toxicity or reduce the plasma concentration at a sub-therapeutic level. This is one of the dangerous types of drug-drug interactions, but predictable & preventable. The CYPs get induced by three nuclear receptors, including the aryl hydrocarbon receptor (AhR); constitutive androstane receptor (CAR); the pregnane X receptor (PXR). Without identification during drug development, enzyme induction phenomenon of a new drug molecule may get noticed only during pharmacovigilance. Though, this CYP induction may not be a barrier for drug development, it may cause possible DDI and treatment failure. According to FDA guidelines, pharmaceutical industries adopted In-vitro, Ex-vivo and In-vivo techniques based on different developmental stages. The results are also interpreted based on regulatory bodies guidelines. For In-vitro assay best accepted method is using primary hepatocytes either fresh or cryopreserved, for Ex-vivo liver slices of different species and in-vivo, clinical investigations are the extreme option. This paper reviews current industry approaches of CYP induction assays to evaluate potentiality for a new drug molecule as an inducer.

The global severity of COVID-19 remains high which results anxiety and other mental health problems, also it altered people's everyday lives, affected human connections and economic operations. The goal of this comprehensive review was to identify the effects of the linkage COVID-19 pandemic on the mental health of different groups and communities. This study compiled evidences of a link between anxiety rates and the COVID-19 pandemic. The evaluation period started in June’ 2022 and ended on August’2022, during this time, total four databases such as PubMed, Science Direct, Tailor & Francis Online, and Springer were used to search scientific literatures. A total 616 studies were identified from all four databases and 63 scientific literatures were selected based of predetermined criteria for review which were published in between 2020 to 2022. Three groups of population such as general population, students and healthcare professionals were taken for review the findings from the selected literatures. Gender, physical disorders, psychiatric disorders, COVID infection, infection rates in colleagues or family members, experience of frontline work & non-frontline work, close contact with infected patients, high exposure risk, quarantine experience, etc. were highly considered as factors associated with increased prevalence of anxiety among all three groups. During the COVID-19 pandemic, the general population, healthcare professionals, and students experienced an increase in the prevalence of mental diseases, whereas infected individuals had a decrease. Females were highly prevalent to anxiety than male. Our comprehensive review concluded significant co-relation between anxiety and COVID-19 but long-term study is needed to better understand which may define the population's mental condition in future.