Advances in Pharmacological and Pharmaceutical Sciences最新文献

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.

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 (p=0.006) 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.

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.

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.

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.

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.

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.

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.

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 (γ_XAE/FL = 0.502), Xylopia aethiopica extract/imipramine (γ_XAE/IP = 0.322), Xylopia aethiopica extract/venlafaxine (γ_XAE/VL = 0.601), xylopic acid/imipramine (γ_XA/IP = 0.556), xylopic acid/venlafaxine (γ_XA/VL = 0.451), and xylopic acid/fluoxetine (γ_XA/FL = 0.298) combinations, which may be potentially due to elevation of serotonergic neurotransmission via varying mechanisms. The AUC of imipramine (AUC_IP = 1966 ± 58.98 µg/ml.h) was significantly (P < 0.0001) reduced by Xylopia aethiopica extract (AUC_IP = 1228 ± 67.40 µg/ml.h) and xylopic acid (AUC_IP = 1250 ± 55.95 µg/ml.h), while the AUC of xylopic acid (AUC_XA = 968.10 ± 61.22 µg/ml.h) was significantly (P < 0.0001) reduced by venlafaxine (AUC_XA = 285.90 ± 51.92 µg/ml.h) and fluoxetine (AUC_XA = 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.

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.