Pharmaceutical Biology最新文献

Context: Pyrus calleryana Decne (Rosaceae), renowned for its therapeutic properties, is known to moisturize the lungs (removing dryness; relieving cough), clear heat (acting as an antipyretic; febrifuge) and aid in detoxification (relieving pyogenic inflammation; eliminating toxins). However, scientific evidence supporting its efficacy in wound healing is lacking.

Objective: This study investigated P. calleryana samples collected over a year to explore metabolite variations and their impact on skin wound-healing activities.

Materials and methods: P. calleryana (PC) twigs and leaves were collected from the Matsu Islands, Taiwan, spanning 2018-2020. Extracts were prepared using 95% ethanol or water, and we assessed the chemical composition, total phenolic/triterpenoid contents and antioxidant properties. Metabolites were analysed via LC-MS/MS and molecular networking. Wound healing potential was evaluated on WS-1 cells through MTT and migration assays, and gene expression analyses, with tests including control (DMSO), compounds 1 (3'-hydroxylbenzyl-4-hydroxybenzoate-4'-O-β-glucopyranoside) and 2 (vanilloylcalleryanin) (100 µM), and a positive control (ascorbic acid, 100 µM) for 24 h.

Results: Significant variations in extract compositions were observed based on the solvent used, with distinct metabolomic profiles in extracts collected during different months. Notably, compounds 1 and 2 showed no cytotoxic effects on human dermal fibroblast cells and significantly accelerated wound closure at 100 μM. A gene expression analysis indicated upregulation of wound healing-associated genes, including MMP-1 (matrix metalloproteinase-1) and COL1A1 (collagen, type 1, alpha 1).

Conclusions: This study reports the first evidence of PC compounds aiding wound healing. Utilizing Global Natural Products Social Molecular Networking (GNPS) and principal component analysis (PCA) approaches, we unveiled metabolomic profiles, suggesting the potential to expedite wound-healing.

Context: Tabersonine has been investigated for its role in modulating inflammation-associated pathways in various diseases. However, its regulatory effects on triple-negative breast cancer (TNBC) have not yet been fully elucidated.

Objective: This study uncovers the anticancer properties of tabersonine in TNBC cells, elucidating its role in enhancing chemosensitivity to cisplatin (CDDP).

Materials and methods: After tabersonine (10 μM) and/or CDDP (10 μM) treatment for 48 h in BT549 and MDA-MB-231 cells, cell proliferation was evaluated using the cell counting kit-8 and colony formation assays. Quantitative proteomics, online prediction tools and molecular docking analyses were used to identify potential downstream targets of tabersonine. Transwell and wound-healing assays and Western blot analysis were used to assess epithelial-mesenchymal transition (EMT) phenotypes.

Results: Tabersonine demonstrated inhibitory effects on TNBC cells, with IC₅₀ values at 48 h being 18.1 μM for BT549 and 27.0 μM for MDA-MB-231. The combined treatment of CDDP and tabersonine synergistically suppressed cell proliferation in BT549 and MDA-MB-231 cells. Enrichment analysis revealed that the proteins differentially regulated by tabersonine were involved in EMT-related signalling pathways. This combination treatment also effectively restricted EMT-related phenotypes. Through the integration of online target prediction and proteomic analysis, Aurora kinase A (AURKA) was identified as a potential downstream target of tabersonine. AURKA expression was reduced in TNBC cells post-treatment with tabersonine.

Discussion and conclusions: Tabersonine significantly enhances the chemosensitivity of CDDP in TNBC cells, underscoring its potential as a promising therapeutic agent for TNBC treatment.

Context: The mechanism of Renshen Shouwu Decoction (RSSW) in treating Alzheimer's disease (AD) remains unknown.

Objective: This study investigates the effects and mechanism of RSSW for ameliorating AD.

Materials and methods: Ten SAMR1 mice and 40 SAMP8 mice were divided into five groups: control (SAMR1), model (SAMP8), positive drug (Donepezil, 1.3 mg/kg/d), and RSSW (Low-dose, 117 mg/kg/d; High-dose, 234 mg/kg/d). Starting from 6 months of age, the medications were administered intragastrically for a total of 60 days. Subsequently, memory improvement in rapidly aging mice was assessed using the novel object recognition test and Morris water maze test. Through the identification of absorbed blood components and analysis of network pharmacology, active ingredients and potential targets involved in the treatment of AD were identified. Finally, AD-related biological indicators were detected using western blotting and ELISA.

Result: Our results demonstrated that RSSW effectively ameliorated memory impairments, inhibited tau hyperphosphorylation, and reduced β-amyloid plaque deposition in SAMP8 mice. Thirty absorbed blood components in RSSW were identified, revealing identified 96 major targets that play a key role in alleviating AD. Notably, the obtained main targets were highly enriched in SIRT1-mediated signaling pathways. Subsequent experimental validation confirmed that RSSW activated the SIRT1/NF-κB, SIRT1/AMPK, and SIRT1/p53 signaling cascades. Nine potential active ingredients were predicted through molecular docking.

Discussion and conclusions: Our research findings suggest the mechanism of RSSW treatment for AD, which ameliorates memory impairments by reducing cortical tissue inflammation and apoptosis.

Context: Although pharmaceutical equipment and medical supplies play a vital role in the quality of traditional medicines, they have not received much attention from stakeholders and researchers nationally and internationally.

Objective: This study assesses traditional healers' knowledge and utilization of pharmaceutical equipment and medical supplies in the Amhara region, North West Ethiopia.

Materials and methods: A quantitative cross-sectional study was conducted on 70 traditional healers. The data were collected using an interview-based questionnaire. The collected data were checked and entered into Statistical Package for Social Sciences version 25.0 for analysis. The results were presented as percentages. The association between socio-demographic characteristics and traditional healers' knowledge of pharmaceutical equipment and medical supplies was examined using Pearson's Chi-squares test.

Results: About 90% of traditional healers had information about pharmaceutical equipment and medical supplies, and currently 80% of them used different pharmaceutical equipment and medical supplies individually and in combination with traditional equipment. Although most traditional healers used different pharmaceutical equipment and medical supplies, only 13.3% of them used equipment and supplies a day. Only 15% of traditional healers continuously cleaned their equipment. None of the socio-demographic variables were significantly associated to the knowledge of pharmaceutical equipment and medical supplies.

Discussion and conclusions: Pharmaceutical equipment and medical supplies used by traditional healers was inconsistent, mainly associated with their habit of using self-prepared and home-available equipment. Moreover, the checkup status of compounding equipment was poor. As Traditional healers provide high-patient care services, emphasis should be given to improving their preparation and treatment strategies.

Context: The botanical species Bauhinia guianensis Aublet (Leguminosae-Cercidoideae) is traditionally used in the Amazon for medicinal purposes.

Objective: The acute toxicity of the hydroethanolic extracts from B. guianensis leaves and stems (HELBg and HESBg) was evaluated in zebrafish (Danio rerio), with emphasis on the embryonic developmental stage and adult alterations.

Materials and methods: Extracts were analyzed on LC-DAD-MS/MS. Zebrafish eggs were inoculated individually with concentrations of HELBg and HESBg (0.25, 0.5, 0.75, 1.0, and 1.5 µg/mL), observed for 96 h. Adult zebrafish were treated with a single oral dose (100, 200, 500, 1000, and 2000 mg/kg) of HELBg and HESBg, observed for 48 h.

Results: HELBg and HESBg analysis detected 55 compounds. Both extracts exhibited toxicity, including embryo coagulation at higher doses of HELBg and absence of heartbeats in embryos at all doses of HESBg. Behavioral variations were observed; tissue alterations in adult zebrafish were found at the highest doses, primarily in the liver, intestine, and kidneys because of HELBg and HESBg effects. The LD₅₀ of HESBg was 1717 mg/kg, while HELBg exceeded the limit dose of 2000 mg/kg.

Conclusions: The study on acute toxicity of B. guianensis extracts exhibits significant toxic potential, emphasizing effects on embryonic and adult zebrafish. The results suggest relative safety of the species preparations, encouraging further clinical trials on potential biological activities.

Context: The effect of the active ingredients in traditional Chinese medicines on the activity of cytochrome P450 enzymes (CYP450s) is a critical factor that should be considered in TCM prescriptions. Physcion, the major active ingredient of Rheum spp. (Polygonaceae), possesses wide pharmacological activities.

Objectives: The effect of physcion on CYP450 activity was investigated to provide a theoretical basis for use.

Materials and methods: The experiments were conducted in pooled human liver microsomes (HLMs). The activity of CYP450 isoforms was evaluated with corresponding substrates and probe reactions. Blank HLMs were set as negative controls, and typical inhibitors were employed as positive controls. The inhibition model was fitted with Lineweaver Burk plots. The concentration (0, 2.5, 5, 10, 25, 50 and 100 μM physcion) and time-dependent (0, 5, 10, 15 and 30 min) effects of physcion were also assessed.

Results: Physcion suppressed CYP2C9, 2D6 and 3A4 in a concentration-dependent manner with IC₅₀ values of 7.44, 17.84 and 13.50 μM, respectively. The inhibition of CYP2C9 and 2D6 was competitive with the K_i values of 3.69 and 8.66 μM, respectively. The inhibition of CYP3A4 was non-competitive with a K_i value of 6.70 μM. Additionally, only the inhibition of CYP3A4 was time-dependent with the K_I and K_inact parameters of 3.10 μM^-1 and 0.049 min^-1, respectively.

Conclusions: The inhibition of CYP450s by physcion should be considered in its clinical prescription, and the study design can be employed to evaluate the interaction of CYP450s with other herbs.

Context: Rice bran arabinoxylan compound (RBAC) is a natural immunomodulator with anticancer properties.

Objective: This study critically evaluates the available evidence on the biological pathways of RBAC and its effects on cancer treatment.

Methods: This secondary analysis of a scoping review includes studies evaluating the mechanisms of RBAC on healthy or malignant cells, animal models, or humans for cancer prevention or treatment. Data from randomized controlled trials on survival and quality of life outcomes were subjectd to meta analysis.

Results: The evidence synthesis was based on 38 articles. RBAC exhibited antitumor properties by promoting apoptosis and restoring immune function in cancer patients to enhance inflammatory and cytotoxic responses to block tumorigenesis. RBAC works synergistically with chemotherapeutic agents by upregulating drug transport. In a clinical trial, combining RBAC with chemoembolization in treating liver cancer showed improved response, reduced recurrence rates, and prolonged survival. RBAC also augments the endogenous antioxidant system to prevent oxidative stress and protect against radiation side effects. In addition, RBAC has chemoprotective effects. Animals and humans have exhibited reduced toxicity and side effects from chemotherapy. Meta analysis indicates that RBAC treatment increases the survival odds by 4.02-times (95% CI: 1.67, 9.69) in the first year and 2.89-times (95% CI: 1.56, 5.35) in the second year.

Conclusion: RBAC is a natural product with immense potential in cancer treatment. Additional research is needed to characterize, quantify, and standardize the active ingredients in RBAC responsible for the anticancer effects. More well-designed, large-scale clinical trials are required to substantiate the treatment efficacies further.

Context: Menhaden fish oil (FO) is widely recognized for inhibiting neuroinflammatory responses and preserving brain function. Nevertheless, the mechanisms of FO influencing brain cognitive function in diabetic states remain unclear.

Objective: This study examines the potential role of FO in suppressing LPS-induced neuroinflammation and cognitive impairment in diabetic animals (DA).

Materials and methods: Thirty male Wistar rats were divided into 5 groups: i) DA received LPS induction (DA-LPS); ii) DA received LPS induction and 1 g/kg FO (DA-LPS-1FO); iii) DA received LPS induction and 3 g/kg FO (DA-LPS-3FO); iv) animals received normal saline and 3 g/kg FO (NS-3FO) and v) control animals received normal saline (CTRL). Y-maze test was used to measure cognitive performance, while brain samples were collected for inflammatory markers and morphological analysis.

Results: DA received LPS induction, and 1 or 3 g/kg FO significantly inhibited hyperglycaemia and brain inflammation, as evidenced by lowered levels of pro-inflammatory mediators. Additionally, both DA-LPS-1FO and DA-LPS-3FO groups exhibited a notable reduction in neuronal damage and glial cell migration compared to the other groups. These results were correlated with the increasing number of entries and time spent in the novel arm of the Y-maze test.

Discussion and conclusion: This study indicates that supplementation of menhaden FO inhibits the LPS signaling pathway and protects against neuroinflammation, consequently maintaining cognitive performance in diabetic animals. Thus, the current study suggested that fish oil may be effective as a supporting therapy option for diabetes to avoid diabetes-cognitive impairment.