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- Prevalence of Self-Medication Practice and Associated Factors among
Pregnant Women Who Attended Antenatal Care at Public Hospitals of North
Shewa Zone, Amhara Region, Ethiopia
Abstract: Background. Self-medication practice is the use of medicine without consulting health professionals to treat self-recognized illness by the general population including pregnant women. Inappropriate self-medication practice during pregnancy may pose harmful consequences for the fetus as well as the mother. There is not given much attention on the practice of self-medication among pregnant women in our setting. Therefore, this study aimed to assess the prevalence of self-medication practice and associated factors among pregnant women who attended antenatal care at North Shewa Zone public hospitals. Methods. An institution-based cross-sectional study was conducted from June 01, 2022 to July 30, 2022, among 650 pregnant women who attended antenatal care at North Shewa Zone public hospitals. A multistage sampling technique was employed. The questionnaires were pretested. A structured interviewer-administered questionnaire and reviewed medical records were used for data collection. Epi-data version 4.6.2 and SPSS version 20 were utilized for data entry and analysis, respectively. Bivariate and multivariable logistic regression was done to identify associated factors, and values less than 0.05 were considered statistically significant. Results. The prevalence of self-medication practice among pregnant women was 65.38%. Housewives (AOR = 0.097 95% CI 0.030, 0.310), farmers (AOR = 0.117, 95% CI 0.028, 0.493), people with health insurance (AOR = 0.507, 95% CI 0.300, 0.858), and people in preconception care (AOR = 0.038, 95% CI 0.011–0.135) were less likely to practice self-medication, while people with primary education (AOR = 3.00, 95% CI 1.217, 7.435), income less than 3,000 birr (AOR = 5.46, 95% CI 1.41, 21.1), participants in the first (AOR = 4.183, 95% CI 2.12, 8.24) and second trimesters (AOR = 2.05, 95% CI 1.18, 3.56), pregnant women who lived in rural areas (AOR = 1.579, 95% CI 1.103–2.260), and people who previously practiced self-medication (AOR = 8.2, 95% CI 5.04, 13.3) were more likely to practice self-medication. Conclusion. From the present finding, it can be concluded that self-medication among pregnant women is high. Previous self-medication practice, gestation period, educational status, monthly income, no preconception care, no health insurance, being a housewife, farmer, and place of residence were significantly associated with self-medication practice. Therefore, preventive measures such as proper counseling during dispensing, awareness creation programs on preconception care, and enrolling in health insurance programs to minimize the practice of self-medication are necessary.
PubDate: Wed, 07 Aug 2024 09:36:51 +000
- Ethnopharmacological Knowledge and Antioxidant Propensities of Argania
spinosa L. from Morocco
Abstract: This work aims to merge ethnopharmacological knowledge with biochemical analysis to enrich our understanding of the significance of the argan tree (Argania spinosa (L.) Skeels) and to valorize its crucial role in the province of Essaouira (Morocco). First, a survey was conducted using semistructured interviews with 325 informants from Essaouira province between February and April 2023. The interviews covered sociodemographic data and information on argan tree uses, whether for therapeutic, cosmetic, or food purposes (i.e., applications, parts used, preparation, and administration). Second, phenolic extracts were prepared from various parts of the argan tree (i.e., leaves, kernels, nut shells, press cake, and oil) and then assessed for their antioxidant potential to scientifically validate their traditional uses. The evaluation of antioxidant activity focused on their free radical scavenging and reducing capacities, using DPPH and FRAP assays. Findings confirmed the cultural significance of the argan tree for the local population, as well as their strong dependence on its products. Indeed, it was noted that argan-based products are widely favored in traditional cuisine, with a prevalence of 83.4%; Amlou is the most commonly consumed food. Therapeutic and cosmetic applications accounted for 48.6% and 28.0%, respectively, predominantly for treating skin and subcutaneous issues (69.5%) and diabetes (19.7%). Argan oil was the most cited argan product used, often consumed raw (97.5%), followed by almonds (22.8%). Cataplasm (26.1%) and maceration (24.6%) were preferred for argan derivative preparation. External application (50.1%) was the primary administration method, followed by oral consumption (38.1%) and massage (27.7%). For in vitro assays, the argan tree could prove to be a promising source of phenolic compounds, especially in the leaves (>4 times richer than other parts, 231.046 ± 5.090 mg GAE/g DW). DPPH and FRAP tests demonstrated notable antiradical potential and reducing power, concentration-dependent. Leaf-derived phenolic extracts exhibited the highest free radical scavenging potential (IC50 = 0.589 ± 0.005 mg/ml) and the best reducing capacity (IC50 = 0.420 ± 0.005 mg/ml), although these potencies remained below the standard used. This study represents valuable documentation that can serve to preserve information on the use of argan products while exploring their phytochemical and pharmacological properties.
PubDate: Mon, 29 Jul 2024 14:48:44 +000
- Deciphering In Vitro and In Vivo Pharmacological Properties of Seed and
Fruit Extracts of Flacourtia jangomas (Lour.) Raeusch
Abstract: The objective of the study was to evaluate the pharmacological properties of the methanolic extract of Flacourtia jangomas (Lour.) Raeusch fruits (PFJM) and seeds (SFJM), along with their soluble fractions in ethyl acetate (fruit: PFJE; seed: SFJE) and chloroform (fruit: PFJC; seed: SFJC). Our phytochemical analysis of the examined extracts confirmed the presence of various therapeutically active phytoconstituents, including flavonoids, tannins, glycosides, and alkaloids. Employing the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical quenching method, SFJC exhibited the highest antioxidative potential, with an IC50 of 48.84, compared to ascorbic acid (IC50 21.77). The thrombolytic activity was assessed through rapid clot analysis of human blood samples, revealing that SFJC demonstrated the highest thrombolytic activity (60.99 ± 2.28%) compared to streptokinase (72.89 ± 2.19%). In the protein denaturation antiarthritic test, the PFJE and SFJC extracts exhibited significant potency, achieving results of 74.28 ± 1.16% and 79.25 ± 0.83%, respectively, at a dose of 500 μg/mL. All samples displayed notable anthelmintic activity by reducing Pheretima posthuma paralysis and death time in a dose-dependent manner compared to albendazole. In both in vivo analgesic tests, SFJC demonstrated substantial () pain inhibition percentages (tail immersion: 49.46%; acetic acid writhing: 66.43%) at a dose of 600 mg/kg. During neuropharmacological screening, all extracts significantly () and dose-dependently decreased the mice’s locomotion activity and motor balance. In the thiopental-induced sedation assay, SFJC significantly decreased the sleep latency time (4.18 ± 0.24 min) and increased the duration of sleep time (85.20 ± 2.39 min) at a higher dose. All samples notably reduced blood glucose levels in the oral glucose tolerance test in a dose-responsive manner, and SFJC exhibited a considerable hypoglycemic impact (7.38 ± 0.44 mmoles/L at 600 mg/kg). The frequency of diarrheal episodes in mice during the antidiarrhea assessment was significantly decreased by the tested plant samples. These findings can serve as a reference for future endeavors to isolate pure bioactive compounds from this plant for the development of novel phytomedicines.
PubDate: Fri, 26 Jul 2024 16:33:48 +000
- Antiallergic Effect of the Alpha-Cyclodextrin Moringin Complex in Rat
Basophilic Leukaemia (RBL-2H3) Cell Line
Abstract: Allergic diseases (ADs) are a major concern when it comes to public well-being. Moringa oleifera Lam is a tropical plant that is used in traditional medicine due to the presence of isothiocyanate. The present study investigated the antiallergic properties of 4-(α-L-rhamnopyranosyloxy)-benzyl isothiocyanate or moringin isolated from Moringa oleifera seeds in the form of alpha-cyclodextrin-moringin (α-CD/MG) complex on rat basophilic leukaemia (RBL-2H3) cell line at both the early and late stages of an allergic reaction. The α-CD/MG complex was initially elucidated using nuclear magnetic resonance (NMR) followed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt proliferation assay to evaluate the cytotoxicity and cell viability with respect to ketotifen fumarate (KF) and α-CD/MG. The release of beta-hexosaminidase (β-hexosaminidase) and histamine was used to determine the level of inhibition in the early stage while the suppression of the release of prostaglandin (PGD2), tumour necrosis factor-alpha (TNF-α), and interleukin (IL-4) was considered in the late stage. Higher concentrations of α-CD/MG (5 μM, ) in mast cell degranulation significantly inhibited the expression of β-hexosaminidase, histamine, TNF-α, PGD2, and IL-4 in both the early and late stages. Thus, α-CD/MG can potentially be developed as an antiallergic drug as it has the ability to inhibit allergic responses in the late and early stages.
PubDate: Thu, 25 Jul 2024 12:03:45 +000
- Cyclophosphamide Pharmacogenomic Variation in Cancer Treatment and Its
Effect on Bioactivation and Pharmacokinetics
Abstract: Cyclophosphamide (Cy) is a prodrug that is mainly bioactivated by cytochrome P450 (CYP) 2B6 enzyme. Several other enzymes are also involved in its bioactivation and affect its kinetics. Previous studies have shown the effect of the enzymes’ genetic polymorphisms on Cy kinetics and its clinical outcome. These results were controversial primarily because of the involvement of several interacting enzymes in the Cy metabolic pathway, which can also be affected by several clinical factors as well as other drug interactions. In this review article, we present the effect of CYP2B6 polymorphisms on Cy kinetics since it is the main bioactivating enzyme, as well as discussing all previously reported enzymes and clinical factors that can alter Cy efficacy. Additionally, we present explanations for key Cy side effects related to the nature and site of its bioactivation. Finally, we discuss the role of busulphan in conditioning regimens in the Cy metabolic pathway as a clinical example of drug-drug interactions involving several enzymes. By the end of this article, our aim is to have provided a comprehensive summary of Cy pharmacogenomics and the effect on its kinetics. The utility of these findings in the development of new strategies for Cy personalized patient dose adjustment will aid in the future optimization of patient specific Cy dosages and ultimately in improving clinical outcomes. In conclusion, CYP2B6 and several other enzyme polymorphisms can alter Cy kinetics and consequently the clinical outcomes. However, the precise quantification of Cy kinetics in any individual patient is complex as it is clearly under multifactorial genetic control. Additionally, other clinical factors such as the patient’s age, diagnosis, concomitant medications, and clinical status should also be considered.
PubDate: Thu, 27 Jun 2024 13:04:59 +000
- Structural Characters and Pharmacological Activity of Protopanaxadiol-Type
Saponins and Protopanaxatriol-Type Saponins from Ginseng
Abstract: Ginseng has a long history of drug application in China, which can treat various diseases and achieve significant efficacy. Ginsenosides have always been deemed important ingredients for pharmacological activities. Based on the structural characteristics of steroidal saponins, ginsenosides are mainly divided into protopanaxadiol-type saponins (PDS, mainly including Rb1, Rb2, Rd, Rc, Rh2, CK, and PPD) and protopanaxatriol-type saponins (PTS, mainly including Re, R1, Rg1, Rh1, Rf, and PPT). The structure differences between PDS and PTS result in the differences of pharmacological activities. This paper provides an overview of PDS and PTS, mainly focusing on their chemical profile, pharmacokinetics, hydrolytic metabolism, and pharmacological activities including antioxidant, antifatigue, antiaging, immunodulation, antitumor, cardiovascular protection, neuroprotection, and antidiabetes. It is intended to contribute to an in-depth study of the relationship between PDS and PTS.
PubDate: Mon, 24 Jun 2024 12:20:40 +000
- Oleic Acid and Succinic Acid: A Potent Nutritional Supplement in Improving
Hepatic Glycaemic Control in Type 2 Diabetic Sprague–Dawley Rats
Abstract: Nutritional supplements are gaining traction for their effects in mitigating the impacts of various health conditions. In particular, many supplements are being proposed to reduce the impacts of type 2 diabetes (T2D), a metabolic condition that has reached global epidemic proportions. Recently, a supplement of oleic acid (OA) and succinic acid (SA; 1 : 1, w/w) was reported to improve glycaemic control in type 2 diabetic (T2D) Sprague–Dawley (S-D) rats through ameliorating insulin release and sensitivity. Here, we investigate the effects of the supplement (OA and SA) on hepatic and pancreatic function in T2D S-D rats. Eighteen (18) S-D rats were rendered diabetic and were divided into three equal groups: diabetic control, diabetic treatment, and diabetic glibenclamide. Another 12 S-D rats were obtained and served as the normal groups. The animals were treated daily with the vehicle, OA and SA (800 mg/kg body weight (bw); 1 : 1), or glibenclamide (10 mg/kg bw) which served as the positive control. The findings indicated that treatment with the supplement resulted in a 35.69 ± 4.22% reduction () in blood glucose levels (BGL). Analysis of hepatic enzymes depicted that the nutritional supplement reduced the activity of the gluconeogenesis enzyme, glucose-6-phosphatase (G6P) while improved the activity of catabolic enzymes such as glucose-6-phosphate dehydrogenase (G6PD) and pyruvate kinase (PK). Furthermore, the supplement attenuated oxidative stress through restoration of catalase (CAT) and superoxide dismutase (SOD), while reducing malondialdehyde (MDA) levels. Finally, the supplement showed no liver or kidney toxicity and improved the size and number of pancreatic islets of Langerhans, indicating its potential application in treating T2D. The study highlighted that a supplement of the two organic acids may be beneficial in reducing the rate of pathogenesis of type 2 diabetes. Therefore, it may offer therapeutic value as a dietary or nutritional supplement in the approach against diabetes and its complications.
PubDate: Wed, 19 Jun 2024 07:04:13 +000
- Investigation into the Interaction between Penicillin-Resistant and
Penicillin-Susceptible Gonococcal Penicillin-Binding Protein 2 and Target
Phenolic Ligands through Molecular Docking Studies and Structure-Activity
Relationship Analysis
Abstract: Gonococcal infections present a notable public health issue, and the major approach for treatment involves using β-lactam antibiotics that specifically target penicillin-binding protein 2 (PBP2) in Neisseria gonorrhoeae. This study examines the influence of flavonoids, namely, rutin, on the structural changes of PBP2 in both penicillin-resistant (FA6140) and penicillin-susceptible (FA19) strains. The research starts by clarifying the structural effects of certain mutations, such as the insertion of an aspartate residue at position 345 (Asp-345a), in the PBP2. The strain FA6140, which is resistant to penicillin, shows specific changes that lead to a decrease in penicillin binding. These mutations, namely, P551S and F504L, have a significant impact on the pace at which acylation occurs and the stability of the strain under high temperatures. Molecular docking analyses investigate the antibacterial activities of rutin and other phytocompounds, emphasising rutin’s exceptional binding affinity and its potential as an inhibitor of PBP2. Quercetin and protocatechuic acid have encouraging antibacterial effectiveness, with quercetin displaying characteristics similar to those of drugs. Molecular dynamics simulations offer a detailed comprehension of the interactions between flavonoids and PBP2, highlighting rutin’s exceptional antioxidant effects and strong affinity for the substrate binding site. The study’s wider ramifications pertain to the pressing requirement for antiviral treatments, namely, in the context of the ongoing COVID-19 epidemic. Flavonoids have a strong affinity for binding to PBP2, indicating their potential as inhibitors to impair cell wall formation in N. gonorrhoeae. Ultimately, this study provides extensive knowledge on the interactions between proteins and ligands, the dynamics of the structure, and the ability of flavonoids to combat penicillin-resistant N. gonorrhoeae bacteria. The verified simulation outcomes establish a basis for the creation of potent inhibitors and medicinal therapies to combat infectious illnesses.
PubDate: Wed, 12 Jun 2024 08:19:05 +000
- Low-Frequency Sonophoresis: A Promising Strategy for Enhanced Transdermal
Delivery
Abstract: Sonophoresis is the most approachable mode of transdermal drug delivery system, wherein low-frequency sonophoresis penetrates the drug molecules into the skin. It is an alternative method for an oral system of drug delivery and hypodermal injections. The cavitation effect is thought to be the main mechanism used in sonophoresis. The cavitation process involves forming a gaseous bubble and its rupture, induced in the coupled medium. Other mechanisms used are thermal effects, convectional effects, and mechanical effects. It mainly applies to transporting hydrophilic drugs, macromolecules, gene delivery, and vaccine delivery. It is also used in carrier-mediated delivery in the form of micelles, liposomes, and dendrimers. Some synergistic effects of sonophoresis, along with some permeation enhancers, such as chemical enhancers, iontophoresis, electroporation, and microneedles, increased the effectiveness of drug penetration. Sonophoresis-mediated ocular drug delivery, nail drug delivery, gene delivery to the brain, sports medicine, and sonothrombolysis are also widely used. In conclusion, while sonophoresis offers promising applications in diverse fields, further research is essential to comprehensively elucidate the biophysical mechanisms governing ultrasound-tissue interactions. Addressing these gaps in understanding will enable the refinement and optimization of sonophoresis-based therapeutic strategies for enhanced clinical efficacy.
PubDate: Wed, 05 Jun 2024 18:34:42 +000
- Characterization of Acid Hydrolyzed Taro Boloso-I (Colocasia esculenta
Cultivar) Starch as a Diluent in Direct Compression of Tablets
Abstract: Corn, wheat, rice, potato, and cassava starches have been widely used as pharmaceutical excipients. However, the search for cost-effective local starch alternatives is necessary due to the availability and usage constraints. In Ethiopia, various plant species, including Taro Boloso-I, have been explored as potential sources of pharmaceutical starch. It is a variety of Colocasia esculenta with a high tuber yield and high starch content. However, the native starch requires modifications to enhance its functionality. Therefore, this study aimed to improve the native starch through acid modification and evaluate its performance as a direct compressible tablet excipient. The native starch was treated with a 6% w/v HCl solution for 192 hours, resulting in acid-modified Taro Boloso-I starch, which was then evaluated for suitability for direct compression. XRD patterns of both the native and modified starch showed characteristic A-type crystals, with significantly higher relative crystallinity observed in the latter. Additionally, the acid-modified starch exhibited a lower moisture content and improved flow properties. The compaction study also demonstrated its improved compactibility (tensile strength: 16.82 kg/cm2), surpassing both the native starch (13.17) and Starch 1500® (11.2). The modified starch also showed a lower lubricant sensitivity compared to the native starch and Starch 1500®. Furthermore, paracetamol tablets made with the modified starch exhibited higher mechanical strength and lower friability in all paracetamol concentrations. It incorporated up to 40% paracetamol while maintaining acceptable tablet characteristics, whereas the native starch and Starch 1500® were limited to 30% (w/w). Based on these findings, the modified starch showed promise as an alternative direct compressible excipient in tablet manufacturing.
PubDate: Wed, 29 May 2024 14:20:00 +000
- Impact of Methods of Preparation on Mechanical Properties, Dissolution
Behavior, and Tableting Characteristics of Ibuprofen-Loaded Amorphous
Solid Dispersions
Abstract: This study aims to improve the biopharmaceutical, mechanical, and tableting properties of a poorly soluble drug, ibuprofen (IBP), by preparing amorphous solid dispersion (ASD) followed by a sustained-release tablet formulation. A suitable polymer to develop an ASD system was chosen by utilizing the apparent solubility of IBP in various polymer solutions. ASDs containing various ratios of IBP and selected polymer were prepared by the melt fusion (MF) method. ASD containing optimized drug-polymer ratio prepared by freeze-drying (FD) method was characterized and compared physicochemically. The solubility of IBP in water increased 28-fold and 35-fold when formulated as ASD by MF and FD, respectively. Precise formulations showed amorphization of IBP and increased surface area, improving solubility. The dissolution pattern of optimized ASD-IBP in pH 6.8 phosphate buffer after 60 min in MF and FD was enhanced 3-fold. In addition, direct compression tablets comprising optimized ASD granules from MF and FD were made and assessed using compendial and noncompendial methods. ASD-IBP/MF and ASD-IBP/FD formulations showed a similar drug release profile. In addition, 12 h of sustained IBP release from the ASD-IBP-containing tablets was obtained in a phosphate buffer with a pH of 6.8. From the dissolution kinetics analysis, the Weibull model fitted well. The drug release pattern indicated minimal variations between tablets formed using ASD-IBP prepared by both procedures; however, pre- and postcompression assessment parameters differed. From these findings, the application of ASD and sustained-release polymers in matrix formation might be beneficial in improving the solubility and absorption of poorly soluble drugs such as IBP.
PubDate: Tue, 28 May 2024 11:05:00 +000
- Exploring the Formulation and Approaches of Injectable Hydrogels Utilizing
Hyaluronic Acid in Biomedical Uses
Abstract: The characteristics of injectable hydrogels make them a prime contender for various biomedical applications. Hyaluronic acid is an essential component of the matrix surrounding the cells; moreover, hyaluronic acid’s structural and biochemical characteristics entice researchers to develop injectable hydrogels for various applications. However, due to its poor mechanical properties, several strategies are used to produce injectable hyaluronic acid hydrogel. This review summarizes published studies on the production of injectable hydrogels based on hyaluronic acid polysaccharide polymers and the biomedical field’s applications for these hydrogel systems. Hyaluronic acid-based hydrogels are divided into two categories based on their injectability mechanisms: in situ-forming injectable hydrogels and shear-thinning injectable hydrogels. Many crosslinking methods are used to create injectable hydrogels; chemical crosslinking techniques are the most frequently investigated technique. Hybrid injectable hydrogel systems are widely investigated by blending hyaluronic acid with other polymers or nanoparticulate systems. Injectable hyaluronic acid hydrogels were thoroughly investigated and proven to demonstrate potential in various medical fields, including delivering drugs and cells, tissue repair, and wound dressings.
PubDate: Mon, 27 May 2024 14:50:01 +000
- Cellulose- and Saccharide-Based Orally Dispersible Thin Films Transform
the Solid States and Dissolution Characteristics of Poorly Soluble
Curcumin
Abstract: This study aimed at developing and optimizing the orally dispersible thin film (ODTF) containing a plant-derived drug—curcumin (CUR). CUR belongs to a biopharmaceutical classification system (BCS) class IV compound that requires improving its water solubility and tissue permeability preceding formulation. An ODTF was applied to produce a solid dispersion matrix for CUR to resolve such solubility and permeability problems. The film-forming polymers used in the study were cellulose-based (hydroxypropyl methylcellulose/HPMC and carboxymethylcellulose/CMC) and saccharide-based maltodextrin (MDX). Poloxamer (POL) was also employed as surfactant and solubilizer. The solvent casting technique was applied to produce the films. The ethanolic solution of CUR was mixed with an aqueous solution of POLs and then incorporated into different film-forming polymers prior to casting. The processing of the CUR with POL solution was intended to aid in the even dispersion of the drug in the polymeric matrices and enhance the wettability of the films. The physical state and properties of the films were characterized in terms of their morphology, crystallinity of the drug, and phase miscibility of the mixtures. The dissolution profile of the films was also evaluated in terms of dissolution rate and dissolution efficiency. The obtained ODTF products were smooth and flat-surfaced. Physical characterization also indicated that the CUR was homogeneously dispersed in the ODTFs and no longer existed as crystalline material as revealed by X-ray diffraction (XRD). The CUR was also not phase-separated from the films as disclosed by differential scanning calorimetry (DSC). Such dispersion was achieved through the solubilizing effect of POLs and compact polymeric film matrices that prevented the CUR from recrystallization. Furthermore, the ODTFs also improved the dissolution of CUR by 3.2-fold higher than the raw CUR. Overall, cellulose-based films had favorable physical properties compared with saccharide-based films.
PubDate: Mon, 27 May 2024 11:05:01 +000
- Investigation of Herb-Drug Interactions between Xylopia aethiopica, Its
Principal Constituent Xylopic Acid, and Antidepressants
Abstract: Introduction. Depression affects an estimated 350 million people worldwide and is implicated in up to 60% of suicides. Only about 60–70% of patients respond to antidepressant therapy. One of the factors causing patients to not attain therapeutic goals is herb-drug interactions. Objective. To investigate any potential herb-drug interaction that might exist between Xylopia aethiopica extract (XAE) or xylopic acid (XA) and selected conventional antidepressants (imipramine, fluoxetine, and venlafaxine) in mice. Methods. Dried, powdered fruits of Xylopia aethiopica were cold macerated in 70% ethanol to obtain XAE. XA was isolated by cold macerating dried fruits of Xylopia aethiopica in petroleum ether, crystallising impure XA with ethyl acetate, and purifying XA crystals with 96% ethanol. Pharmacodynamic interaction was assessed via isobolographic analysis of tail suspension tests of the agents individually and in their respective combinations. Pharmacokinetic interaction was assessed by monitoring the effect of coadministrations on the plasma concentration of antidepressants and xylopic acid via HPLC analysis. Results. XAE and XA in mice showed significant antidepressant-like activity in the tail suspension test. With interaction indices less than one, synergism of antidepressant effect was observed in the Xylopia aethiopica extract/fluoxetine ( = 0.502), Xylopia aethiopica extract/imipramine ( = 0.322), Xylopia aethiopica extract/venlafaxine ( = 0.601), xylopic acid/imipramine ( = 0.556), xylopic acid/venlafaxine ( = 0.451), and xylopic acid/fluoxetine ( = 0.298) combinations, which may be potentially due to elevation of serotonergic neurotransmission via varying mechanisms. The AUC of imipramine (AUCIP = 1966 ± 58.98 µg/ml.h) was significantly () reduced by Xylopia aethiopica extract (AUCIP = 1228 ± 67.40 µg/ml.h) and xylopic acid (AUCIP = 1250 ± 55.95 µg/ml.h), while the AUC of xylopic acid (AUCXA = 968.10 ± 61.22 µg/ml.h) was significantly () reduced by venlafaxine (AUCXA = 285.90 ± 51.92 µg/ml.h) and fluoxetine (AUCXA = 510.60 ± 44.74 µg/ml.h), possibly due to the effect of interfering agents on gastric emptying hence reducing oral absorption. Conclusion. Xylopia aethiopica extract and xylopic acid interacted synergistically with imipramine, fluoxetine, and venlafaxine and reduced the systemic circulation of imipramine.
PubDate: Sat, 25 May 2024 11:05:00 +000
- Development of White Cabbage, Coffee, and Red Onion Extracts as Natural
Phosphodiesterase-4B (PDE4B) Inhibitors for Cognitive Dysfunction: In
Vitro and In Silico Studies
Abstract: Human cognition fundamentally depends on memory. Alzheimer’s disease exhibits a strong correlation with a decline in this factor. Phosphodiesterase-4 B (PDE4B) plays a crucial role in neurodegenerative disorders, and its inhibition is one of the promising approaches for memory enhancement. This study aimed to identify secondary metabolites in white cabbage, coffee, and red onion extracts and identify their molecular interaction with PDE4B by in silico and in vitro experiments. Crushed white cabbage and red onion were macerated separately with ethanol to yield respective extracts, and ground coffee was boiled with water to produce aqueous extract. Thin layer chromatography (TLC)–densitometry was used to examine the phytochemicals present in white cabbage, coffee, and red onion extracts. Molecular docking studies were performed to know the interaction of test compounds with PDE4B. TLC-densitometry analysis showed that chlorogenic acid and quercetin were detected as major compounds in coffee and red onion extracts, respectively. In silico studies revealed that alpha-tocopherol (binding free energy () = −38.00 kcal/mol) has the strongest interaction with PDE4B whereas chlorogenic acid ( = −21.50 kcal/mol) and quercetin ( = −17.25 kcal/mol) exhibited moderate interaction. In vitro assay showed that the combination extracts (cabbage, coffee, and red onion) had a stronger activity (half-maximal inhibitory concentration (IC50) = 0.12 ± 0.03 µM) than combination standards (sinigrin, chlorogenic acid, and quercetin) (IC50 = 0.17 ± 0.03 µM) and rolipram (IC50 = 0.15 ± 0.008 µM). Thus, the combination extracts are a promising cognitive enhancer by blocking PDE4B activity.
PubDate: Tue, 21 May 2024 02:20:00 +000
- Apicoplast-Resident Processes: Exploiting the Chink in the Armour of
Plasmodium falciparum Parasites
Abstract: The discovery of a relict plastid, also known as an apicoplast (apicomplexan plastid), that houses housekeeping processes and metabolic pathways critical to Plasmodium parasites’ survival has prompted increased research on identifying potent inhibitors that can impinge on apicoplast-localised processes. The apicoplast is absent in humans, yet it is proposed to originate from the eukaryote’s secondary endosymbiosis of a primary symbiont. This symbiotic relationship provides a favourable microenvironment for metabolic processes such as haem biosynthesis, Fe-S cluster synthesis, isoprenoid biosynthesis, fatty acid synthesis, and housekeeping processes such as DNA replication, transcription, and translation, distinct from analogous mammalian processes. Recent advancements in comprehending the biology of the apicoplast reveal it as a vulnerable organelle for malaria parasites, offering numerous potential targets for effective antimalarial therapies. We provide an overview of the metabolic processes occurring in the apicoplast and discuss the organelle as a viable antimalarial target in light of current advances in drug discovery. We further highlighted the relevance of these metabolic processes to Plasmodium falciparum during the different stages of the lifecycle.
PubDate: Fri, 10 May 2024 09:20:00 +000
- Alpha-Glucosidase Inhibition, Antioxidant Activities, and Molecular
Docking Study of Krom Luang Chumphon Khet Udomsak, a Thai Traditional
Remedy
Abstract: Krom Luang Chumphon Khet Udomsak remedy (KKR) has traditionally been used as an alternative treatment, particularly for hyperglycemia; however, its therapeutic efficacy has not been scientifically validated. Thus, this study aims to investigate the potential inhibitory and antioxidant effects of α-glucosidase enzyme and characterize the chemical profile of KKR extracts using gas chromatography-mass spectrometry (GC-MS). The investigation highlights both KKR extracts as potent inhibitors of α-glucosidase, with the ethanolic extract of KKR (KKRE) displaying an IC50 value of 46.80 µg/mL and a noncompetitive mode of action. The combination of ethanolic and aqueous extracts of KKR (KKRE and KKRA, respectively) with acarbose exhibited a synergistic effect against the α-glucosidase. The KKRE extract displayed strong scavenging effects in the DPPH assay (IC50 156.3 µg/mL) and contained significant total phenolic (172.82 mg GAE/g extract) and flavonoid (77.41 mg QE/g extract) contents. The major component of KKRE is palmitic acid (15.67%). Molecular docking revealed that the major compounds interacted with key amino acid residues (ASP215, GLU277, HIS351, ASP352, and ARG442), which are crucial for inhibiting α-glucosidase. Notably, campesterin had a more significant influence on α-glucosidase than acarbose, with low binding energy. These findings underscore the significance of KKR in traditional medicine and suggest that it is promising treatment for diabetes mellitus. Further studies using animal model will provide valuable insights for advancing this research.
PubDate: Tue, 30 Apr 2024 08:05:01 +000
- 6-Octadecenoic and Oleic Acid in Liquid Smoke Rice Husk Showed COVID-19
Inhibitor Properties
Abstract: In recent years, liquid smoke rice husk (LSRH) has shown its therapeutic potency to diabetes, wound healing, stomatitis, and periodontitis. The phenol, 6-octadecenoic acid, oleic acid, and 9-octadecanoic acid were responsible for their therapeutic effect. The LSRH also demonstrated their potential for infectious diseases such as coronavirus disease (COVID-19). Therefore, the molecular dynamics (MDs) simulation and pharmacophore analysis was performed to analyse the binding stability of 6-octadecenoic and oleic acid. Based on MD simulation, 6-octadecenoic and oleic acids seemed to retain their interactions with Ser144 and Thr24, respectively, with hydrogen bond distance less than 2.9 Å. This interaction was stable during the simulation and has hydrophobic and hydrogen bonds/acceptors. The 6-octadecenoic acid and oleic acid were confirmed to have great potency as inhibitors for COVID-19. These compounds also showed that the existence of hydrophobic and hydrogen bonds/acceptors could increase biological activity.
PubDate: Thu, 25 Apr 2024 07:20:00 +000
- System Pharmacological Approach to Investigate and Validate Multitargeted
and Therapeutic Effect of Furocoumarins of Apium graveolens L. for
Treatment of Kidney Disease
Abstract: Background. System pharmacological approaches play important roles in drug discovery and development and in biomolecular exploration to investigate the multitarget therapeutic effects of phytochemicals for the treatment of acute and chronic ailments. Objectives. The aim of the study was to apply a system pharmacological approach to investigate the multitarget therapeutic effects of furocoumarins of Apium graveolens L. for the treatment of kidney disease. Methods. Several furocoumarins of Apium graveolens were screened from online databases. Network biology and poly-pharmacology analyses were performed to investigate the multitarget therapeutic effect of furocoumarins. The potential metabolites that showed significant interactions with various genes were selected for in silico docking analysis with CASP-3 and SOD proteins. In silico ADME analysis was also performed to investigate the pharmacokinetic behavior of targeted furocoumarins. Results. Out of thirteen furocoumarins selected for analysis, six showed partial or significant interaction with SOD and CASP-3 proteins. These metabolites may alleviate kidney dysfunction by reducing oxidative and inflammatory stress, regulating apoptosis, slowing down the progression of diabetic nephropathy, and reducing hypertension and glomerular vascular rigidity. In silico docking analysis revealed bergapten as a potential therapeutic agent for kidney disease treatment. In silico docking analysis showed anglicine, imperatorin, and sphondin exhibited strong interaction with CASP-3 and SOD with binding energy −6.5, −7.2, −6.5 and −6.8, −6.2 −5.7 kcal/mol, respectively. These components exhibited greater conventional hydrogen bonding with CASP-3 and SOD than other furocoumarins. Furthermore, in silico ADME analysis of metabolites showed that all furocoumarins have a highly lipophilic nature, good skin permeability, and GI absorption, as well as good blood-brain permeability (BBB). Conclusion. Furocoumarins reduce kidney dysfunction and associated pathophysiological complications via the reduction of glomerular vascular rigidity, diabetic nephropathy, and oxidative and inflammatory stress. However, further biomolecular and clinical examinations are necessary to validate and enhance the credibility of present findings.
PubDate: Wed, 17 Apr 2024 10:35:01 +000
- Ethanol Extract of Ampelopsis brevipedunculata Rhizomes Suppresses
IgE-Mediated Mast Cell Activation and Anaphylaxis
Abstract: More than 20% of the world’s population suffers from allergic diseases, including allergic asthma, rhinitis, and atopic dermatitis that severely reduce the patient’s quality of life. The treatment of allergy has been developed, but there are still unmet needs. Ampelopsis brevipedunculata (Maxim.) Trautv. is a traditional medicinal herb with beneficial bioactivities, such as antioxidant, anti-hypertension, anti-viral, anti-mutagenic, and skin and liver (anti-hepatotoxic) protective actions. However, its anti-allergic effect has not been addressed. This study designed to investigate the pharmacological effect of an ethanol extract of A. brevipedunculata rhizomes (ABE) on mast cell and anaphylaxis models. For in vivo studies, we used ovalbumin-induced active systemic anaphylaxis (ASA) and immunoglobulin (Ig) E-mediated passive cutaneous anaphylaxis (PCA) models. In ASA model, oral administration of ABE (1, 10, and 100 mg/kg) attenuated the anaphylactic responses, such as hypothermia, serum histamine, and IgE productions. In PCA model, ABE also suppressed the plasma extravasation and swelling. The underlying mechanisms of action were identified in various mast cell types. In vitro, ABE (10, 30, and 60 µg/mL) inhibited the release of essential allergic mediators, such as histamine and β-hexosaminidase, in a concentration-dependent manner. ABE prevented the rapid increase in intracellular calcium levels induced by the DNP-HSA challenge. In addition, ABE downregulated the tumor necrosis factor-α and interleukin-4 by suppressing the activation of nuclear factor-κB. Collectively, this study is the first to identify the anti-allergic effect of ABE, suggesting that ABE is a promising candidate for treating allergic diseases.
PubDate: Thu, 04 Apr 2024 12:05:01 +000
- Synthesis, Molecular Docking, Molecular Dynamic Simulation Studies, and
Antitubercular Activity Evaluation of Substituted Benzimidazole
Derivatives
Abstract: Tuberculosis, also known as TB, is a widespread bacterial infection that remains a significant global health issue. This study focuses on conducting a thorough investigation into the synthesis, evaluation of anti-Tb activity, molecular docking, and molecular dynamic simulation of substituted benzimidazole derivatives. A series of twelve substituted benzimidazole derivatives (1–12) were successfully synthesized, employing a scaffold consisting of electron-withdrawing and electron-donating groups. The newly synthesized compounds were defined by their FTIR, 1H NMR, and mass spectra. The microplate Alamar blue assay (MABA) was used to evaluate the antimycobacterial activity of the synthesized compound against Mycobacterium tuberculosis (Mtb). Compounds 7 (MIC = 0.8 g/mL) and 8 (MIC = 0.8 g/mL) demonstrated exceptional potential to inhibit M. tuberculosis compared to the standard drug (isoniazid). In addition, the synthesized compounds were docked with the Mtb KasA protein (PDB ID: 6P9K), and the results of molecular docking and molecular dynamic simulation confirmed the experimental results, as compounds 7 and 8 exhibited the highest binding energy of −7.36 and −7.17 kcal/mol, respectively. The simulation results such as the RMSD value, RMSF value, radius of gyration, and hydrogen bond analysis illustrated the optimum potential of compounds 7 and 8 to inhibit the M. tuberculosis strain. Hydrogen bond analysis suggested that compound 7 has greater stability and affinity towards the KasA protein compared to compound 8. Moreover, both compounds (7 and 8) were safe for acute inhalation and cutaneous sensitization. These two compounds have the potential to be potent M. tuberculosis inhibitors.
PubDate: Thu, 28 Mar 2024 11:50:01 +000
- Investigating the Presence of Falsified and Poor-Quality Fixed-Dose
Combination Artemether-Lumefantrine Pharmaceutical Dosage Forms in Kumasi,
Ghana
Abstract: Artemether-lumefantrine (AL) is a highly effective and commonly used Artemisinin-based Combination Therapy (ACT) for treating uncomplicated malaria caused by Plasmodium falciparum, including drug-resistant strains. However, ineffective regulatory systems in resource-limited settings can lead to the infiltration of poor-quality and counterfeit antimalarial medicines into the pharmaceutical supply chain, causing treatment failures, prolonged illness, and disease progression. The objective of the study was to assess the quality of selected brands of fixed-dose combination (FDC) AL tablets and suspensions marketed in Kumasi, Ghana. A total of fourteen brands of FDC AL medicines, comprising eight tablets and six suspensions were purchased from various retail pharmacy outlets in Kumasi, Ghana. All samples were subjected to thorough visual inspection as a quick means of checking quality through meticulous observation of the packaging or dosage form. The quality parameters of the tablets were determined using uniformity of weight, hardness, friability, and disintegration tests. Suspensions were assessed based on pH and compared with the British Pharmacopeia (BP) standard. The samples were then analyzed for drug content (assay) using reverse-phase high-performance liquid chromatography (RP-HPLC). All the tablet samples conformed to BP specification limits for uniformity of weight (deviation of less than ± 5%), hardness (4.0–10 kg/mm2), friability (
PubDate: Mon, 25 Mar 2024 11:50:01 +000
- In Vitro Antibacterial, DPPH Radical Scavenging Activities, and In Silico
Molecular Modeling of Isolated Compounds from the Roots of Clematis
hirsuta
Abstract: Clematis hirsuta is one of the traditional medicinal plants used in Ethiopia to treat different ailments, such as cancer and diseases related to the respiratory system. This study aimed to isolate the phytochemical components of the root of C. hirsuta and evaluate their in vitro and in silico biological activities. Oleic acid (1), palmitic acid (2), sterols (3 and 4), boehmenan (5), and carolignans E (6 and 7) were isolated by silica gel column chromatography and preparative thin layer chromatography and characterized by NMR spectroscopy. Compounds 5–7 were isolated from the plant for the first time. At 5 mg/mL, the inhibition zone of evaluated compounds ranged from 8.80 to 11.10 mm against all selected bacteria. The MIC of the MeOH and n-hexane: EtOAc (1 : 1) extracts was greater than or equal to 50 mg/mL against all selected bacteria. At 62.5 μg/mL, the % DPPH radical scavenging activity of tested compounds ranged from 30.3% to 92.1% with an IC50 value of 19.4 to 2.1 μg/mL. The results of molecular docking studies indicated that the docking scores of compounds 3–7 ranged from −6.4 to −7.9 kcal/mol against E. coli DNA gyrase B, −8.3 to −9.0 kcal/mol against the Pseudomonas quinolone signal A, −7.1 to −8.5 kcal/mol against pyruvate kinase M2, and −7.9 to −8.5 kcal/mol against human topoisomerase IIβ. The results of the in silico antibacterial activity of compounds 3, 5, and 6 supported the in vitro antibacterial test results. Compound 5 had a better docking score against human topoisomerase IIβ than the other test samples demonstrating its potential as an anticancer agent. Therefore, compounds 3–7 could be considered as a lead for developing antibacterial and anticancer drugs. Moreover, the presence of these active phytochemicals supports the traditional use of this plant against cancer and bacteria.
PubDate: Mon, 25 Mar 2024 09:20:00 +000
- Brucine Entrapped Titanium Oxide Nanoparticle for Anticancer Treatment: An
In Vitro Study
Abstract: Backgroundand Objective. The public’s health has been seriously threatened by cervical cancer during recent times. In terms of newly diagnosed cases worldwide, it ranks as the ninth most prevalent malignancy. Multiple investigations have proven that nanoparticles can effectively combat cancer due to their small dimensions and extensive surface area. In the meantime, bioactive compounds which are biocompatible are being loaded onto nanoparticles to promote cancer therapy. The current study investigates the anticancerous potential of Brucine-entrapped titanium oxide nanoparticles (TiO2 NPs) in cervical cancer cell line (HeLa). Materials and Methods. The physiochemical, structural, and morphological aspects of Brucine-entrapped TiO2 NPs were evaluated by UV-visible spectrophotometer, Fourier transform-infrared spectroscopy (FT-IR), dynamic light scattering (DLS), scanning electron microscopy (SEM), and energy dispersive X-ray (EDAX). The cytotoxic effect against the HeLa cell line was assessed using a tetrazolium-based colorimetric assay (MTT), a trypan blue exclusion (TBE) assay, phase contrast microscopic analysis, and a fluorescence assay including ROS and DAPI staining. Furthermore, estimation of antioxidant markers includes catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD). Results. The UV spectrum at 266 nm revealed the formation of TiO NPs. The FT-IR peaks confirmed the effective entrapment of brucine with TiO2 NPs. The average size (100.0 nm) of Brucine-entrapped TiO2 NPs was revealed in DLS analysis. The micrograph of the SEM revealed the formation of ellipsoidal to tetragonal-shaped NPs. The Ti, O, and C signals were observed in EDAX. In MTT assay, Brucine-entrapped TiO2 NPs showed inhibition of cell proliferation in a dose-wise manner and IC50 was noticed at the concentration of 30 µg/mL. The percentage of viable cells gradually reduced in the trypan blue exclusion assay. The phase contrast microscopic analysis of Brucine-entrapped TiO2 NP-treated cells showed cell shrinkage, cell wall deterioration, and cell blebbing. The intracellular ROS level was increased in a dose-wise manner when compared to control cells in ROS staining. The condensed nuclei and apoptotic cells were increased in treated cells, as noted in DAPI staining. In treated cells, the antioxidant markers such as CAT, GSH, and SOD levels were substantially lower compared to the control cells. Conclusion. The synthesized Brucine entrapped TiO2 NPs exhibited remarkable anticancer activity against the HeLa cell line.
PubDate: Mon, 18 Mar 2024 06:35:01 +000
- Antibacterial and Antioxidant Activities of Triterpenoids Isolated from
Endemic Euphorbia arbuscula Stem Latex
Abstract: This research study aimed to investigate the chemical constituents and evaluate the antibacterial and antioxidant activities of stem latex extracts from the endemic medicinal plant Euphorbia arbuscula found on Socotra Island, Yemen. The study aimed to assess the potential medicinal and veterinary uses of this plant, representing the first evaluation of its properties. The stem latex was extracted using ethanol, and the resulting oil underwent analysis using GC-MS to identify eight compounds. In addition, chromatographic techniques were employed to isolate two triterpenoids, lanosterol and lupeol, from the stem latex. The structures of these compounds were confirmed using IR, MS, and NMR techniques. The antibacterial activity of the extracts and isolated compounds was evaluated against three bacterial strains using the disc diffusion method, revealing only weak antibacterial effects. The study also investigated the antioxidant activity using the DPPH assay, where the ethyl acetate extract exhibited the highest activity with an IC50 value of ±13.55 µg/mL, followed by the chloroform extract with an IC50 of ±21.87 µg/mL. These findings emphasize the potential of Euphorbia arbuscula in the development of new medicines, particularly due to its notable antioxidant activity. The research methodology employed a scientifically rigorous approach, utilizing a comprehensive range of analytical techniques. However, further investigation is required to fully assess the plant’s potential as a therapeutic agent.
PubDate: Sat, 09 Mar 2024 02:05:01 +000
- Suppression of Inflammation in Adipocyte-Macrophage Coculture by Passion
Fruit Seed Extract: Insights into the p38 and NF-ҡB Pathway
Abstract: Obesity, which is characterized by chronic low-grade inflammation, involves the infiltration of immune cells into adipose tissue, leading to the secretion of inflammatory cytokines and subsequent inflammation. Therefore, the aim of this study was to examine the potential of passion fruit seed extract (PSEE) in mitigating lipopolysaccharide (LPS)-induced inflammation in a coculture system comprising macrophages and adipocytes. PSEE demonstrated significant reductions in reactive oxygen species (ROS) and nitric oxide (NO) levels, primarily achieved through the downregulation of inducible nitric oxide synthase (iNOS) protein expression in LPS-induced adipocyte-macrophage cocultures. Furthermore, PSEE effectively suppressed the secretion of TNF-α and IL-1β by attenuating the gene expression of these cytokines, as well as other inflammation-related genes such as MMP-2, IL-6, and MCP-1. Notably, PSEE exhibited potent inhibitory effects on the p38 and NF-κB signaling pathways, thus alleviating inflammation in the LPS-induced adipocyte-macrophage cocultures. Additionally, PSEE led to a decrease in the expression of ACC, HSL, and FaSN, while aP2 and ATGL showed increased expression in LPS-induced cocultured macrophages and adipocytes. These findings suggest that passion fruit seed extract effectively combats inflammation by suppressing the p38 and NF-κB signaling pathways, resulting in reduced levels of proinflammatory cytokines, NO, and ROS production.
PubDate: Sat, 09 Mar 2024 01:35:00 +000
- Cardiovascular Protective Effect of Garcinia dulcis Flower Acetone Extract
in 2-Kidney-1-Clip Hypertensive Rats
Abstract: Morelloflavone and camboginol are bioactive compounds purified from Garcinia dulcis (GD), which has anti-inflammatory and antihypertensive properties. The objective of this study was to examine the cardiovascular protective effect of GD flower acetone extract in 2-kidney-1-clip (2K1C) hypertensive rats. Male Wistar rats underwent 2K1C or sham operation (SO) and were housed for 4 weeks. Each group of rats, then, was further divided into 2 subgroups receiving oral administration of either 50 mg/kg BW GD extract or corn oil (vehicle) daily for 4 weeks. Noninvasive blood pressure (BP) and body weight were measured weekly throughout the study. Subsequently, the invasive measurement of arterial BP and the heart rate were determined in all anesthetized rats. The baroreceptor reflex sensitivity (BRS) was investigated by injection of either phenylephrine or sodium nitroprusside for bradycardia or tachycardia response, respectively. Histological examination of the heart and thoracic aorta was also performed in order to investigate the general morphology and the tumor necrosis factor alpha (TNF-α) expression. We found that the GD flower extract significantly diminished the BP and restored the impaired BRS. Moreover, it also decreased the TNF-α expression in the cardiac muscle and thoracic aorta of 2K1C when compared to the SO group. Taken together, our data showed that GD flower extract exhibits the cardiovascular protective effect in the 2K1C hypertensive rats.
PubDate: Thu, 29 Feb 2024 04:05:01 +000
- The Effect of Clopidogrel and Ticagrelor on Human Adipose Mesenchymal Stem
Cell Osteogenic Differentiation Potential: In Vitro Comparative Study
Abstract: Ticagrelor (TICA) and clopidogrel (CLP) are extensively used antiplatelet drugs that act by antagonizing the P2Y12 receptors that are found on platelets in addition to bone cells. Aim. The purpose of this study was to investigate the effect of clopidogrel and ticagrelor on stem cells osteogenic differentiation in vitro. Methods. Human adipose-derived mesenchymal stem cells (hAd-MSCs) were divided into (1) control group, (2) osteogenic group (osteo group), (3) clopidogrel group (CLP group), and (4) ticagrelor group (TICA group). The osteogenic differentiation potential was determined by mineralization nodule formation using Alizarin Red S staining, measuring ALP enzyme activity by alkaline phosphatase assay. Quantitative determination for osteogenic markers included osteocalcin (OC); runt-related transcription factor 2 (RUNX2) performed using western blot; osteoprotegerin (OPG) using enzyme-linked immunosorbent assay (ELISA) and inflammatory markers; and tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) measured using real-time polymerase chain reaction quantitative (RT-PCR) and ELISA. Results. In comparison to all study groups, the TICA group showed significant increase in the mineralized extracellular matrix, ALP enzyme activity, and bone markers expression as RUNX2 (), OC, and OPG (). The expression of IL-6 and TNF-α was determined by RT-qPCR and ELISA techniques. TICA and CLP significantly decreased both markers compared to the control group. The TICA group showed statistically significant lower levels of both markers () than the CLP and control groups via the ELISA technique. Conclusion. TICA may possess a positive effect on hAd-MSCs osteogenic differentiation compared to CLP.
PubDate: Thu, 15 Feb 2024 10:50:01 +000
- Structure Identification and Risk Assurance of Unknown Impurities in
Pramipexole Oral Drug Formulation
Abstract: Impurities compounds in any pharmaceutical product or drug substance are inevitable from a chemistry point of view. The quality and safety of a pharmaceutical product are also significantly affected by these impurities content; therefore, impurities need to be identified and characterized through the use of appropriate analytical methods. Pramipexole is a nonergot dopamine agonist used to treat various Parkinson’s disease symptoms. Two unknown impurities were detected from a pramipexole dihydrochloride solid dosage form. These impurities were identified and characterized using ultra-performance liquid chromatography coupled with high-resolution mass spectroscopy (UPLC-HRMS). These impurities were found to be enriched when mannitol existed in the formulation. The structure and mechanism involved in the existence of the impurities were proposed. Furthermore, observation of the binding affinity potential risk of these impurities to the pramipexole receptor has also been demonstrated through molecular docking and molecular dynamics simulation study. The binding energy result showed that pramipexole interaction with dopamine receptors D2 and D3 was higher than pramipexole mannose adduct and pramipexole ribose adduct.
PubDate: Tue, 13 Feb 2024 12:05:01 +000
- Suppression of Migration and Invasion by
4-Carbomethoxyl-10-Epigyrosanoldie E from the Cultured Soft Coral
Sinularia sandensis through the MAPKs Pathway on Oral Cancer Cells
Abstract: The primary reason for cancer-related fatalities is metastasis. The compound 4-carbomethoxyl-10-epigyrosanoldie E, derived from the Sinularia sandensis soft coral species grown in cultures, exhibits properties that counteract inflammation. Moreover, it has been observed to trigger both apoptosis and autophagy within cancerous cells. This research focuses on examining the inhibitory impact of 4-carbomethoxyl-10-epigyrosanoldie E on the migration and invasion processes in Cal-27 and Ca9-22 oral cancer cell lines. To assess how this compound affects cell migration and invasion, the Boyden chamber assay was employed. Furthermore, Western blot analysis was utilized to explore the underlying molecular mechanisms. In a dose-dependent manner, 4-carbomethoxyl-10-epigyrosanoldie E notably decreased the levels of matrix metalloproteinase-2 (MMP-2) and MMP-9, along with urokinase-type plasminogen activator (uPA), in both Cal-27 and Ca9-22 cell lines. Conversely, it elevated the concentrations of tissue inhibitors of metalloproteinases-1 (TIMP-1) and TIMP-2. In addition, the treatment with this compound led to the inhibition of phosphorylation in extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). It also curtailed the expression of several key proteins including focal adhesion kinase (FAK), protein kinase C (PKC), growth factor receptor-bound protein 2 (GRB2), Rac, Ras, Rho A, mitogen-activated protein kinase kinase kinase 3 (MEKK3), and mitogen-activated protein kinase kinase 7 (MKK7). Furthermore, the expression levels of IQ-domain GTPase-activating protein 1 (IQGAP1) and zonula occludens-1 (ZO-1) were significantly reduced by the compound. The ability of 4-carbomethoxyl-10-epigyrosanoldie E to inhibit the migration and invasion of Cal-27 and Ca9-22 oral cancer cells was observed to be dose dependent. This inhibitory effect is primarily attributed to the suppression of MMP-2 and MMP-9 expression, as well as the downregulation of the mitogen-activated protein kinase (MAPK) signaling pathway.
PubDate: Mon, 12 Feb 2024 11:35:02 +000
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