Advances in Pharmacological and Pharmaceutical Sciences

Objective. Phenolic acids are well-known phytochemicals that are detected in a wide variety of medicinal plants, and their antiproliferative effects on cancer cells are known, but their mechanisms are poorly revealed. In most of cancer cells, telomerase reverse transcriptase (hTERT) is a dominant factor of telomere length regulation. The hTERT expression promotes invasiveness in tumor cells and is a hallmark of cancer. Therefore, in this study, the probable inhibitory effects of caffeic (Caf), coumaric (Cum), and ferulic acids (Fer) are investigated on the hTERT expression pattern in HepG2 cells. Methods. The MTT, apoptosis assays, and real-time PCR analysis were applied to evaluate viability, cytotoxicity, and hTERT gene expression level, respectively. Results. All of the studied phenolic acids showed cytotoxic effects on HepG2 cells in a timely manner and presented a time-dependent inhibitory effect on the growth of HepG2 cells. They reduced percentage of viable cells and induced apoptosis. Also, these phenolic acids had significant inhibitory effects on hTERT gene expression. Conclusion. These findings suggest that cell viability along with hTERT gene expression in HepG2 cells could be reduced by Cum, Caf, and Fer. As different cancer cells are resistant to conventional chemotherapeutics, this type of results proposes the telomerase as a proper target of cancer therapy development by natural products.

Solid dispersions have achieved significant interest as an effective means of enhancing the dissolution rate and thus the bioavailability of a range of weakly water-soluble drugs. Solid dispersions of weakly water-soluble drugs with water-soluble carriers have lowered the frequency of these problems and improved dissolution. Solid dispersion is a solubilization technology emphasizing mainly on, drug-polymer two-component systems in which drug dispersion and its stabilization is the key to formulation development. Therefore, this technology is recognized as an exceptionally useful means of improving the dissolution properties of poorly water-soluble drugs and in the latest years, a big deal of understanding has been accumulated about solid dispersion, however, their commercial application is limited. In this review article, emphasis is placed on solubility, BCS classification, and carriers. Moreover, this article presents the diverse preparation techniques for solid dispersion and gathers some of the recent technological transfers. The different types of solid dispersions based on the carrier used and molecular arrangement were underlined. Additionally, it summarizes the mechanisms, the methods of preparing solid dispersions, and the marketed drugs that are available using solid dispersion approaches.

African trypanosomiasis is a major neglected tropical disease with significant health and economic concerns in sub-Saharan Africa. In the absence of vaccines for African trypanosomiasis, there is a consideration for alternative sources of chemotherapy. Acanthospermum hispidum DC (A. hispidum) is a herbal species of the Asteraceae family that is endowed with rich phytochemicals with unknown mechanisms of antitrypanosomal effects. This study aimed to investigate the cellular mechanisms of antitrypanosomal and antioxidant activities of A. hispidum against Trypanosoma brucei (T. brucei), a causative protozoan species of African trypanosomiasis. Fractions were prepared from the whole plant of A. hispidum through solvent partitioning by employing solvents of varying polarities (hexane, HEX; dichloromethane, DCM; ethyl acetate, EA; aqueous, AQ). The in vitro efficacies and mechanisms of antitrypanosomal activities of A. hispidum were investigated using a panel of cell biological approaches. GC-MS analysis was used to identify the major compounds with a possible contribution to the trypanocidal effects of A. hispidum. A. hispidum fractions displayed significant antitrypanosomal activities in terms of half-maximal effective concentrations (EC₅₀) and selectivity indices (SI) (AH-HEX, EC₅₀ = 2.4 μg/mL, SI = 35.1; AH-DCM, EC₅₀ = 2.2 μg/mL, SI = 38.3; AH-EA, EC₅₀ = 1.0 μg/mL, SI = 92.8; AH-AQ, EC₅₀ = 2.0 μg/mL, SI = 43.8). Fluorescence microscopic analysis showed that at their EC₅₀ values, the fractions of A. hispidum altered the cell morphology as well as the organization of the mitochondria, nucleus, and kinetoplast in T. brucei. At their maximum tested concentrations, the prepared fractions exhibited antioxidant absorbance intensities comparable to the reference antioxidant, Trolox, in contrast to the oxidant intensity of an animal antitrypanosomal drug, diminazene (Trolox, 0.11 A; diminazene, 0.65 A; AH-HEX, 0.20 A, AH-DCM, 0.20 A, AH-EA, 0.13 A, AH-AQ, 0.22 A). GC-MS analysis of the various fractions identified major compounds assignable to the group of alkaloids and esters or amides of aliphatic acids. The results provide useful pharmacological insights into the chemotherapeutic potential of A. hispidum toward drug discovery for African trypanosomiasis.

Background. Plants are a rich source of therapeutic compounds that have tremendous applications in the pharmaceutical industry. This study aimed to identify the phytochemicals present in the seven selected medicinal plants as well as their antioxidant and antimicrobial activities. Methods. Phytochemical screening, total phenolic, and flavonoid contents were determined using standard methods. The antioxidant activity of plant extracts was determined using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl (OH), and nitric oxide (NO) radical scavenging assays. The antimicrobial activity of the plant extracts was determined by the broth microdilution method. Results. The results of phytochemical analysis showed the presence of phenols, flavonoids, and steroids in all plant extracts. The extract of Psychotria peduncularis showed the highest total phenolic and flavonoid contents (5.57 ± 0.22 mg GAE/g and 1.38 ± 0.06 mg QE/g, respectively). All plant extracts showed very strong antioxidant activity against DPPH and NO radical scavenging with IC₅₀ values ranging from 0.55 to 49.43 µg/mL and 0.65 to 13.7 µg/mL, respectively. The extracts of Tristemma mauritianum and P. peduncularis displayed significant antibacterial activity with MIC values ranging from 16 to 1024 µg/mL. T. mauritianum extract showed bactericidal activity against all tested species. The extracts of Alsophila manianna and P. peduncularis showed significant antifungal activity (MIC = 64 µg/mL) against Candida albicans strain. Conclusion. The screened extracts of medicinal plants used in our study can be used as potential antioxidant and antimicrobial agents, and resources for the development of new drugs.

Historically, natural products have been the principal source of medications for the treatment of human diseases. Traditional medical practitioners employ Detarium microcarpum as a treatment for diabetes, malaria, wounds, inflammation, and even cancer. This study emphasizes the importance of harmonizing D. microcarpum research so that results from various sources may be directly compared to reach a scientific conclusion. We searched Google Scholar, Science Direct, Google.com, Wiley, PubMed, Hindawi, and Springer for research papers on Detarium microcarpum. This analysis excludes untrustworthy online data, thesis papers, and review publications on D. microcarpum. The leaves and stem bark were shown to have high antioxidant, anti-inflammatory, antibacterial, antidiabetic, and anticancer properties. The study also discovered that too much consumption is harmful. Polyphenols and flavonoids were the most commonly reported compounds. However, human safety and efficacy are yet to be fully evaluated, and further well-designed clinical trials are needed to confirm preclinical findings. The leaves and stem bark extracts and isolated compound mechanism of action should be investigated. It is necessary to set a standard dose and ensure its safety.

Background and Objectives. A wound is one of the high-prevalence disorders that affect people’s lives physically, mentally, and financially. This study examined the Astragalus microcephalus Willd. wound healing process in in vivo and in vitro conditions by focusing on the phytoestrogen activity of this extract. Methods. The methanolic root extract was prepared by maceration, and flavonoids were evaluated by LC/MS. In silico examination was performed based on the LC/MS results, and the binding affinity of these compounds to estrogen receptors (ERs) α and β was evaluated. Wound healing evaluation in both in vitro (NHDF cell line, by 500 μg/ml concentration of the extract, 24 h) and in vivo (Wistar rat, topical daily treated with 1.5% of the extract ointment, 21 days) conditions in comparison to control groups was conducted. Rats’ control groups included silver sulfadiazine, Vaseline, and the nontreated groups. Results. Eleven flavonoids were detected using LC/MS. The in silico study showed that formononetin, kaempferol-based structures, quercetin-3-O-neohesperidoside, and calycosin-7-O-beta-D-glucoside had a high affinity (<−6.3) to ERs α and β. Wound closing measurement showed significant improvement in the group treated with the extract in both in vitro and in vivo assays compared to the control groups. Histopathological results confirmed these findings; inflammation factors decreased, and fibroblast proliferation, fibrosis, and epithelization increased, especially in the extract group. Conclusion. This study shows that Astragalus microcephalus has wound healing activity in vitro and in vivo with low toxicity due to the presence of flavonoids, especially isoflavonoids, which show a high affinity to bind to ERs α and β in the skin tissue.