Pharmaceutical Biology最新文献

Context: Celastrol, acknowledged as a prominent exemplar of the potential for transforming traditional medicinal compounds into contemporary pharmaceuticals, has garnered considerable attention owing to its extensive pharmacological activities. The increasing volume of publications concerning celastrol highlights its importance in current scientific inquiry. Despite the growing interest in this compound, a bibliometric analysis focused on this subject remains to be undertaken.

Objective: Our study explored a bibliometric approach to identify and characterize global research trends and frontiers related to celastrol, including mapping research outputs, influential contributors, and thematic areas, as well as highlighting gaps and opportunities for future investigations.

Materials and methods: In this study, we utilized the Web of Science Core Collection (WoSCC) to source and review articles related to celastrol published from 1997 to 2023. The bibliometric analysis was conducted using the R package 'Bibliometrix,' supplemented by visualization tools including CiteSpace, VOSviewer, and GraphPad Prism 10.

Results: Celastrol related research papers have exhibited an upward trend annually and can be categorized into three distinct phases, each highlighting different areas of focus. China, the United States, and South Korea rank as the top three nations for publication volume, with varied research interests across these countries. Several prolific research teams have emerged, each with distinct areas of interest. Examining the primary research domains of celastrol (anti-inflammatory, anticancer, and toxicity) reveals a notable intersection between the first two domains.

Discussion and conclusions: The scope and depth of celastrol research have been steadily expanding, with regional and team-specific variations. Key research areas include anti-inflammatory, anticancer, and toxicity studies. Future research is expected to focus on enhancing the effectiveness and reducing the toxicity of celastrol. Meanwhile, given the multi-target characteristics of celastrol's effects, integrating methods such as network biology and molecular simulation will provide a novel perspective for celastrol research.

Context: The decline in ovarian reserve is a major concern in female reproductive health, often associated with oxidative stress and mitochondrial dysfunction. Although ginsenoside Rg1 is known to modulate mitophagy, its effectiveness in mitigating ovarian reserve decline remains unclear.

Objective: To investigate the role of ginsenoside Rg1 in promoting mitophagy to preserve ovarian reserve.

Materials and methods: Ovarian reserve function, reproductive capacity, oxidative stress levels, and mitochondrial function were compared between ginsenoside Rg1-treated and untreated naturally aged female Drosophila using behavioral, histological, and molecular biological techniques. The protective effects of ginsenoside Rg1 were analyzed in a Drosophila model of oxidative damage induced by tert-butyl hydroperoxide. Protein expression levels in the PINK1/Parkin pathway were assessed, and molecular docking and PINK1 mutant analyses were conducted to identify potential targets.

Results: Ginsenoside Rg1 significantly mitigated ovarian reserve decline, enhancing offspring quantity and quality, increasing the levels of ecdysteroids, preventing ovarian atrophy, and elevating germline stem cell numbers in aged Drosophila. Ginsenoside Rg1 improved superoxide dismutase, catalase activity, and gene expression while reducing reactive oxygen species levels. Ginsenoside Rg1 activated the mitophagy pathway by upregulating PINK1, Parkin, and Atg8a and downregulating Ref(2)P. Knockdown of PINK1 in the ovary by RNAi attenuated the protective effects of ginsenoside Rg1. Molecular docking analysis revealed that the ginsenoside Rg1 could bind to the active site of the PINK1 kinase domain.

Discussion and conclusions: Ginsenoside Rg1 targets PINK1 to regulate mitophagy, preserving ovarian reserve. These findings suggest the potential of ginsenoside Rg1 as a therapeutic strategy to prevent ovarian reserve decline.

Context: Flavones, the key active components in Traditional Chinese Medicine (TCM), have demonstrated antidepressant activity. Given the numerous animal studies conducted, a systematic analysis is essential to provide a valuable reference for future research.

Object: This study investigated the antidepressant activity of flavones based on animal models and summarized the underlying mechanisms.

Methods: We systematically searched 7 bibliographic Databases as of August 12, 2023, such as Web of Science, PubMed, China National Knowledge Infrastructure, etc. The meta-analysis was performed using either the random or fixed-effect model, supplemented by trial sequential analysis (TSA). The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to assess the quality of evidence.

Results: A total of 25 studies involving 458 mice were included, identifying five flavones (baicalin, baicalein, apigenin, luteolin, vitexin) with antidepressant activity. Compared to the control group, flavones significantly reduced immobility time in forced swimming and tail suspension tests. Flavones also decreased serum and hippocampal levels of interleukin (IL)-1β and tumor necrosis factor-alpha (TNF-α), reduced nuclear factor kappa B (NF-κB) levels, and increased brain-derived neurotrophic factor (BDNF) levels. Relative to the positive group, flavones raised IL-6, sucrose preference rate, and corticosterone (CORT) levels, with no significant differences in other factors. The TSA showed the efficacy of flavones for treating depression with adequate 'information size' for the primary outcome.

Conclusions: The results demonstrate that flavones exert protective effects against depression in mice, primarily by stimulating neurotrophic factors and modulating inflammatory pathways. These findings emphasize their potential as promising candidates for the development of novel antidepressant therapies.

Context: Gansui [Euphorbia kansui T. N. Liou ex S.B.Ho (Euphorbiaceae)] has been reported to inhibit the proliferation of non-small cell lung cancer (NSCLC) cells; however, its underlying pharmacological mechanism remains unclear.

Objective: To investigate the potential effects and mechanisms of Gansui in blocking NSCLC progression.

Materials and methods: The targets of Gansui's components and NSCLC-related targets were obtained through public database and published studies. Functional enrichment analysis was performed using the clusterProfiler R package. STRING database was used for protein-protein interaction analysis. CytoHubba plugin was applied to get the hub genes. Molecular docking was applied to assess the binding affinities between the hub targets and the crucial components. Kidjolanin was used to treat A549 and NCI-H1385, and its effects on cell viability, sensitivity of paclitaxel and expression levels of hub genes were investigated by cell counting kit-8 assay, flow cytometry and qPCR.

Results: A total of 16 Gansui active ingredients and 337 targets were collected, of which 298 targets overlapped with NSCLC-related genes. STAT3, EGFR, GRB2, AKT2, AKT3 and PIK3CA were identified as hub genes. The components in Gansui, including kidjoranin 3-O-β-digitoxopyranoside, cynotophylloside B, 13-Oxyingenol-dodecanoate, and kidjolanin had good binding affinity with the hub targets. Kidjolanin inhibited the viability of NSCLC cells, promoted apoptosis and inhibited the expression of hub genes. Kidjolanin also enhanced the proliferation inhibition and apoptosis of NSCLC cells induced by paclitaxel.

Discussion and conclusion: Gansui exerts anti-NSCLC effects via multiple downstream targets, implying its potential in NSCLC treatment.

Objectives: The aim of this systematic work is a Strengths, Weaknesses, Opportunities, Threats (SWOT) analysis to select suitable medicinal plants for cultivation in the region of Baden-Wuerttemberg, Germany.

Methods: A systematic SWOT analysis, based on expert assesments and literature research, was performed considering factors like market demand, cultivation conditions, and potential economic benefits.

Results: Medicinal plants have been essential for producing compounds with significant health benefits. However, unsuitable harvesting practices threaten plant species and traditional communities due to loss of knowledge and culture. In response, sustainable cultivation is gaining attention as alternative to wild collection, ensuring both biodiversity conversation and integrity of medicinal products. Three plants - Arnica montana L., Hydrastis canadensis L., and Rheum rhaponticum L. - were identified as particularly suitable due to their high demand and feasibility of their cultivation under local conditions. Conversely, six other plants were deemed less viable due to various challenges, including market competition and harvesting difficulties.

Conclusions: This publication emphasizes the importance of comprehensive planning and analysis in transitioning from wild collection to sustainable cultivation of medicinal plants, highlighting the potential benefits for regional agriculture, conservation efforts, and the pharmaceutical industry. BIOPRO Baden-Württemberg GmbH promotes this approach by fostering a bioeconomy centred on cultivating high-value medicinal plants in the state of Baden-Wuerttemberg, Germany.

Context: Qinggong Shoutao Wan (QGSTW) is a pill used as a traditional medicine to treat age-associated memory decline (AAMI). However, its potential mechanisms are unclear.

Objective: This study elucidates the possible mechanisms of QGSTW in treating AAMI.

Materials and methods: Network pharmacology and molecular docking approaches were utilized to identify the potential pathway by which QGSTW alleviates AAMI. C57BL/6J mice were divided randomly into control, model, and QGSTW groups. A mouse model of AAMI was established by d-galactose, and the pathways that QGSTW acts on to ameliorate AAMI were determined by ELISA, immunofluorescence staining and Western blotting after treatment with d-gal (100 mg/kg) and QGSTW (20 mL/kg) for 12 weeks.

Results: Network pharmacology demonstrated that the targets of the active components were significantly enriched in the cAMP signaling pathway. AKT1, FOS, GRIN2B, and GRIN1 were the core target proteins. QGSTW treatment increased the discrimination index from -16.92 ± 7.06 to 23.88 ± 15.94% in the novel location test and from -19.54 ± 5.71 to 17.55 ± 6.73% in the novel object recognition test. ELISA showed that QGSTW could increase the levels of cAMP. Western blot analysis revealed that QGSTW could upregulate the expression of PKA, CREB, c-Fos, GluN1, GluA1, CaMKII-α, and SYN. Immunostaining revealed that the expression of SYN was decreased in the CA1 and DG.

Discussion and conclusions: This study not only provides new insights into the mechanism of QGSTW in the treatment of AAMI but also provides important information and new research ideas for the discovery of traditional Chinese medicine compounds that can treat AAMI.

Context: Chinese medicine injections (CMIs) are widely used as adjuvant therapy for cervical cancer in China. However, the effectiveness of different types of CMIs remains uncertain.

Objective: To assess the effectiveness and safety of CMIs when used in conjunction with radiotherapy (RT) or concurrent chemoradiotherapy (CCRT), particularly in combination with cisplatin (DDP), docetaxel plus cisplatin (DP), and paclitaxel plus cisplatin (TP).

Materials and methods: Randomized controlled trials (RCTs) were searched in databases including CNKI, WanFang, VIP, SinoMed, PubMed, Cochrane Library, Embase, and Web of Science from inception to September 2023. We calculated the risk ratio with a 95% confidence interval and the surface under the cumulative ranking area curve (SUCRA) for the clinical efficacy rate (CER), the efficacy rate by Karnofsky Performance Status (KPS), and the rates of leukopenia reduction (LRR) and gastrointestinal reactions (GRR).

Results: Forty-seven RCTs were included, including nine CMI types: Aidi, Fufangkushen, Huangqi, Kangai (KA), Kanglaite (KLT), Renshenduotang, Shenqifuzheng (SQFZ), Shenmai (SM), and Yadanzi. KLT and KA were likely optimal choices with radiotherapy for CER and KPS, respectively. KA and KLT were optimal choices with RT + DDP for CER and GRR, respectively. KLT was the likely optimal choice with RT + DP for CER and KA for both KPS and GRR. SM and SQFZ were the likely optimal choices with RT + TP for CER and LRR, respectively.

Conclusions: The optimal recommendation depends on whether CMIs are used with radiotherapy or concurrent chemoradiotherapy. More high-quality RCTs are needed to confirm further and update the existing evidence.

Context: Cephaeline is a natural product isolated from ipecac (Cephaelis ipecacuanha [Brot.] A. Rich. [Rubiaceae]). It exhibits promising anti-lung cancer activity and ferroptosis induction may be a key mechanism for its anti-lung cancer effect.

Objectives: This study investigates the anti-lung cancer activity and mechanisms of cephaeline both in vitro and in vivo.

Materials and methods: H460 and A549 lung cancer cells were used. The cephaeline inhibition rate on lung cancer cells was detected via a Cell Counting Kit-8 assay after treatment with cephaeline for 24 h. Subsequently, the concentrations of 25, 50 and 100 nM were used for in vitro experiments. In addition, the antitumour effects of cephaeline (5, 10 mg/kg) in vivo were evaluated after 12 d of cephaeline treatment.

Results: Cephaeline showed significant inhibitory effects on lung cancer cells, and the IC₅₀ of cephaeline on H460 and A549 at 24, 48 and 72 h were 88, 58 and 35 nM, respectively, for H460 cells and 89, 65 and 43 nM, respectively, for A549 cells. Meanwhile, we demonstrated that ferroptosis is the key mechanism of cephaeline against lung cancer. Finally, we found that cephaeline induced ferroptosis in lung cancer cells by targeting NRF2.

Discussion and conclusion: We demonstrated for the first time that cephaeline inhibits NRF2, leading to ferroptosis in lung cancer cells. These findings may contribute to the development of innovative therapeutics for lung cancer.

Context: Jian Gan powder (JGP) is a Chinese medicine compound comprised ginseng, Radix Paeoniae Alba, Radix Astragali, Salvia miltiorrhiza, Yujin, Rhizoma Cyperi, Fructus aurantii, Sophora flavescens, Yinchen, Bupleurum and licorice.

Objective: This study explored the inhibitory effects, polarization and potential mechanisms associated with JGP in macrophages.

Materials and methods: RAW264.7 cells were randomly divided into six groups for 24 h: control, lipopolysaccharide (LPS), overexpression, 1% JGP, 2% JGP, 4% JGP, 8% JGP and 16% JGP. The effects of JGP on RAW264.7 cell proliferation were assessed using colony formation assays and cell counting kit-8 (CCK-8) assays. The Transwell assay was used to evaluate its impact on RAW264.7 cell migration. Moreover, we analysed the interleukin-6 (IL-6)/signal transducer and activator of the transcription 3 (IL-6/STAT3) signaling pathway using quantitative real-time PCR and Western blotting. Furthermore, we examined the M1/M2 polarization levels.

Results: Unlike LPS stimulation, JGP serum treatment markedly suppressed macrophage proliferation and migration capacity, while STAT3 overexpression enhanced RAW264.7 cell proliferation and migration. JGP inhibited the proliferation and migration of RAW264.7 cells by attenuating the IL-6/STAT3 signaling pathway. Furthermore, it inhibited macrophage M1 polarization, promoting M2 polarization.

Discussion and conclusions: JGP effectively suppressed the cellular function of RAW264.7 cells by down-regulating the IL-6/STAT3 signaling pathway and modulating macrophage M1/M2 polarization. These findings provide valuable theoretical and experimental basis for considering the potential clinical application of JGP in the treatment of immune-mediated liver injury in clinical practice.

Context: Plant peptides garner attention for their potential antimicrobial properties amid the rising concern over antibiotic-resistant bacteria.

Objective: This study investigates the antibacterial potential of crude peptide extracts from 27 Thai plants collected locally.

Materials and methods: Peptide extracts from 34 plant parts, derived from 27 Thai plants, were tested for their antimicrobial efficacy against four highly resistant bacterial strains: Streptococcus aureus MRSA, Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli. The stability of these peptide extracts was examined at different temperatures, and the synergistic effects of two selected plant peptide extracts were investigated. Additionally, the time-kill kinetics of the individual extracts and their combination were determined against the tested pathogens.

Results: Peptides from Allium sativum L. and Allium oschaninii O. Fedtsch (Amaryllidaceae) were particularly potent, inhibiting bacterial growth with MICs ranging from 1.43 to 86.50 µg/mL. The consistent MICs and MBCs of these extracts across various extraction time points highlight their reliability. Stability tests reveal that these peptides maintain their antimicrobial activity at -20 °C for over a month, emphasizing their durability for future exploration and potential applications in addressing antibiotic resistance. Time-kill assays elucidate the time and concentration-dependent nature of these antimicrobial effects, underscoring their potent initial activity and sustained efficacy over time.

Discussion and conclusions: This study highlights the antimicrobial potential of Allium-derived peptides, endorsing them for combating antibiotic resistance and prompting further investigation into their mechanisms.