Pharmaceutical and Biomedical Research
Volume:9 Issue: 3, Sep 2023

5-aminolevulinic acid (5-ALA) is the mitochondria metabolite produced from glycine and succinyl-CoA, which is converted to protoporphyrin IX (PpIX) by the conjugation of eight itself molecules forming the “heme” group in a porphyrin ring (Figure 1) [1]. The PpIX is used as a photosensitizer (PS) with an absorption wavelength of 410 nm, and 5-ALA acts as a precursor or prodrug for PpIX in photodynamic therapy (PDT). Exogenous administration of excessive amounts of 5-ALA increases the production of PpIX during heme biosynthesis. It is eliminated after 24-48 h with a lower risk of long-term photosensitivity [2]. However, 5-ALA PDT has several disadvantages, including the concentration of ALA is affected by its absorption and pharmacokinetics that are not fully covered the treatment area [3-5], as well as the limited depth of tumor penetration and caused pain symptoms [6].

Since cannabis has been legally allowed for medicinal purposes in many countries, it has become the most interesting issue, particularly in neurologic disorders, such as Alzheimer’s disease (AD). Inhibition of acetylcholinesterase (AChE) is one of the mechanisms for the treatment of AD.

The present study aimed to establish a method for the preparation of cannabinoid-rich extracts and determine their AChE inhibitory activity.

The cannabinoid-rich extracts were prepared through a green extraction process using microwave-assisted extraction (MAE) followed by hydrophobic column separation. The contents of cannabidiol (CBD) and Δ-9-tetrahydrocannabinol (THC) were determined using high-performance liquid chromatography (HPLC). In vitro AChE inhibitory activity was determined via the photometric method using AChE from Electrophorus electricus.

Three cannabinoids-rich fractions were obtained with different concentrations of CBD and THC, namely Fractions I (CBD of 8.1% w/w; THC of 52.2% w/w), II (CBD of 9.2% w/w; THC of 8.0% w/w), and III (CBD 1.3% w/w, THC 33.5% w/w). These cannabinoid-rich extracts exhibited AChE inhibitory activity, with IC50 values of 52.3, 59.8, and 71.2 µg/mL, respectively.

This finding suggests that CBD, but not THC, might be an active compound contributing to AChE inhibitory effect.

Plantago lanceolata L. (ribwort plantain) and Plantago major L. (broadleaf plantain) are widely used in ethnobotanical studies and for treating various diseases. This study aims to investigate the antimicrobial activity and chemical compounds of these plants.

The leaf extracts of P. lanceolata and P. major were fractioned using different solvents. The phytochemical screening was carried out by the gas chromatography-mass spectrometry (GC-MS) method. The antibacterial activity of extracts was assessed using the disc diffusion method, and the minimum inhibitory concentration (MIC) and the minimum bactericidal concentrations (MBC) were measured by microtiter-broth dilution method.

The dichloromethane leaf extract of P. lanceolata and P. major showed the highest antibacterial activity against Salmonella paratyphi (diameter of the inhibition zone: 18.83 and 20.00 mm, respectively) at 100 mg/mL concentration. The lowest MIC was related to dichloromethane extracts of both plants against S. paratyphi (500 µg/mL). The lowest MBC (1000 µg/mL) was related to the dichloromethane extract of P. major against S. paratyphi. The main compounds of P. lanceolata leaf extracts were bis(2-ethylhexyl) phthalate (41.96%), 1-methoxy-3-(2-hydroxyethyl)nonane (32.69%), bicyclo[3.1.1]heptane, 2,6,6-trimethyl- (1.alpha.,2.beta.,5.alpha.)- (10.45%), and cycloheptasiloxane tetradecamethyl- (27.96% and 31.33%). The main compounds of P. major leaf extracts were eicosane (23.62%), cyclohexasiloxane dodecamethyl- (18.21%), 1-methyl-3-n-propyl-2-pyrazolin-5-one (18.08%), cycloheptasiloxane tetradecamethyl- (33.85%), and 1,2-benzisothiazole-3-acetic acid, methyl ester (34.26%).

Fractionation of the methanolic leaf extract of P. lanceolata and P. major can help better isolate active components from these plants. The antibacterial properties of the extracts of two plants may be due to the presence of antibacterial compounds detected in GC-MS.

The natural origin of medicinal plants does not guarantee their safety, as there are no sufficient studies on the safety, efficacy, and toxicity to support their benefit claims.

This study aimed at investigating the oral acute toxicity of Adansonia digitata L. (A. digitata) fruit shell extract in mice.

The maceration method was employed for the extraction of the A. digitata fruit shell using methanol. The extract was then screened for its phytochemical constituents both qualitatively and quantitatively. Lorke’s method was followed for the toxicity study, and the mice were observed for clinical signs of toxicity and mortality. Further, serum was analyzed for liver and kidney function biomarkers besides the histology of the liver, kidney, and cerebellum.

No single death was recorded and no sign of toxicity persisted for more than 2 hours post-administration to the extracts up to 5000 mg/kg. Therefore, the - of A. digitata fruit shell is above 5000 mg/kg. Additionally, no changes were observed in the weights as well as the relative organ weight of the mice. Further, no statistically significant changes were seen in their liver and kidney function biomarkers, besides the relatively intact histological appearance of their liver, kidney, and cerebellum.

The oral acute toxicity of methanol extract of A. digitata fruit shell is above 5000 mg/kg; hence, it is relatively safe to use it for medicinal purposes. However, a longer study duration is recommended to evaluate its toxic effects on fertility, teratogenicity, and carcinogenic potentials.  

According to COVID-19 mutation and no defined treatment, it is necessary to find effective treatment. Chlorpromazine, a phenothiazine antipsychotic drug, has been shown in animal studies to have antiviral effects by inhibiting clathrin-mediated endocytosis. The aim of this study was to evaluate the effectiveness of adding chlorpromazine to the atazanavir/ritonavir regimen in the treatment of moderate COVID-19 patients.

In this randomized double-blind clinical trial, sixty hospitalized patients with moderate COVID-19 confirmed by CT findings or polymerase chain reaction (PCR) were enrolled. All patients received atazanavir/ritonavir 300mg/100mg once daily. In two parallel groups, chlorpromazine 25 mg three times a day or a placebo was administered for up to 14 days. Complete blood count with differential, C-reactive protein (CRP), liver enzymes, and erythrocyte sedimentation rate was measured on days 1, 3, 5, 7, and 10. The primary outcome was the improvement of oxygen saturation and the secondary outcome was the duration of hospitalization and conversion of PCR test results.

Oxygen saturation during the hospitalization was not different among the two groups. The mean duration of hospitalization in the chlorpromazine group was 7.4±2.7 days and in the placebo was 8.2±3 days (P=0.2). Compared to baseline, both groups showed an increase in white blood cell count (P=0.04) and polymorphonuclear cells (P=0.04) but lymphocyte count decreased. At the end of the study, the PCR test was negative in 100% of patients in the chlorpromazine group and 95% of patients in the placebo group.

In adult hospitalized patients with moderate symptomatic COVID-19, adding chlorpromazine to the atazanavir/ritonavir regimen did not improve outcomes.

In animal studies, minocycline (Mcy) has been proven to have antidepressant effects. In addition to modulating peripheral and central pro-inflammatory pathways, Mcy may regulate the hypothalamic-pituitary-adrenal (HPA) axis and the mechanistic target of rapamycin (mTOR) signaling pathway. This study aims to evaluate the antidepressant-like effect of Mcy in mice following injection of dexamethasone (Dex) or cyclosporine-A (CsA).

Male NMRI mice were randomly divided into eight groups of 6, including control, Dex 0.25 mg/kg, CsA 20 mg/kg, Mcy 40 mg/kg, Dex+Mcy, Dex+fluoxetine 20 mg/kg, CsA+Mcy, and CsA+fluoxetine. All drugs were injected intraperitoneally (except for Dex, which was subcutaneous injection) once daily for 3 days. The locomotor activity, forced swimming test (FST), and sucrose preference (SP) test were performed on day 4.

Mcy alone reduced immobility time in the FST (27.0±6.4 s) compared to the control group (104±3.9 s) (P<0.001). After the co-administration of Mcy and Dex, the immobility time significantly decreased (79.5±6.5 s) compared to the Dex group (P<0.001). It also decreased following the co-administration of Mcy and CsA (67.5±20.8 s) compared to the CsA group (P<0.001). Results were similar in the groups treated with fluoxetine plus Dex or CsA. Significant differences were not observed in the locomotor activity test.

Mcy prevents depression-like behavior in mice during the FST when it is co-administrated with CsA or Dex. The possibility of the positive effect of Mcy on the HPA axis and the mTOR signaling pathway should be examined in further studies.

Patients with type 2 diabetes (T2D) often have other associated comorbidities, making them susceptible to drug-related problems (DRPs) which can adversely affect their quality of life. Understanding these problems can provide baseline data to allow informed health decisions and effective management of patients.

This study aims to investigate DRPs in T2D patients with hypertension and find the predictors of these problems.

This cross-sectional study was conducted for six months in the internal medicine department of a tertiary care hospital in Lebanon. Participants were 135 adult T2D patients with hypertension who were receiving one or more anti-diabetes drugs, and at least one medication for hypertension. Pharmaceutical care network europe classification system was used to classify the DRPs. Data were collected by two clinical pharmacists using a self-report tool.

Most of patients were female. Most of them (94.1%) had at least one DRP (1.43±0.72 per patient). “Non-optimal drug treatment effect” was the most frequent problem (48.2%). Achieving the HbA1C target reduced the odds of this problem by 66.6%, while the increased serum creatinine level caused a two-fold increase in this problem. The use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers reduced the odds of DRPs by 86.2% and 83.3%, respectively, while lipid-lowering and anti-anginal drug use caused a four-fold increase in DRPs.

Early identification of DRPs in diabetic patients with hypertension and their associated factors can help improve their management and reduce the associated mortality and morbidity rates.

Pseudomonas aeruginosa biofilm is one of the problems in antibiotic treatment of infections. Nanomedicines, such as chitosan (CS) can carry multiple drugs and improve the therapeutic effects of antibiotics.

This study aimed at the synthesis and characterization of ciprofloxacin-loaded chitosan nanoparticles for eradication of P. aeroginosa biofilm.

Cipro-CS microparticles were prepared by ionic gelation method and their size, zeta potential, and drug release pattern were determined. MBEC and MBIC of different groups of antibiotics (ciprofloxacin, ciprofloxacin-PAβN, CS ciprofloxacin, and CS ciprofloxacinPAβN) were performed on biofilm samples of P. aeroginosa.

Ciprofloxacin loading efficiency was 35.51%, and encapsulation efficiency was 55.06%. Released ciprofloxacin from CS nanoparticles was 80% after 24 hours. Biofilm production was positive in 96.7% of the isolates while 30.1% of the samples had strong biofilm. The best result for MBIC was CS ciprofloxacin, CS ciprofloxacin-PAβN, ciprofloxacin- PAβN, and ciprofloxacin, respectively. For MBEC the result was slightly different and from the best to better CS Ciprofloxacin-PAβN, CS Ciprofloxacin, Ciprofloxacin-PAβN, and ciprofloxacin.

Today, with increasing antibiotic resistance, there are many challenges in treating infections. Due to the role of biofilm in antibiotic resistance, researchers are looking for new antibiotics to treat infections.