Advances in Pharmacological and Pharmaceutical Sciences

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.

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 (AUC_IP = 1966 ± 58.98 µg/ml.h) was significantly () 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 () 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.

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.

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.

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.

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.