Pharmaceutical Biology最新文献

Context: Naringenin is a natural flavanone with potent pharmacological properties. It has demonstrated therapeutic potential in treating various diseases and organ injuries, including radiation-induced lung injury (RILI). Ferroptosis is a newly type of cell death, and naringenin has been shown to attenuates ferroptosis.

Objective: To evaluate the inhibitory effect and molecular mechanism of naringenin on ferroptosis during RILI process.

Materials & methods: Firstly, BEAS-2B and HUVECs cells were pre-incubated with naringenin for 1 h prior to 8 Gy of X-ray irradiation to evaluate oxidative stress, inflammation, and the mRNA levels of ferroptosis-related genes. Next, target genes of naringenin, RILI, and ferroptosis were identified using the TCMSP, SwissTargetPrediction, and GeneCards databases. The target network was constructed with Cytoscape and STRING. Finally, the core target genes were identified through in vitro experiments by qRT-PCR, western blot and immunofluorescence staining.

Results: Naringenin effectively reduced radiation-induced increasement of oxidative stress, inflammation, and ferroptosis markers in both cell lines. Network pharmacology identified 14 target genes, with prostaglandin endoperoxide synthase (PTGS2) and Valosin-containing protein (VCP) mRNA levels being prominent, which were crucial for ferroptosis regulation. Molecular docking revealed strong binding interactions between naringenin and the two target proteins. Subsequently, experimental validation confirmed that naringenin reduced the elevated levels of PTGS2 and VCP induced by radiation.

Discussion & conclusion: Naringenin alleviates radiation-induced lung damage by inhibiting ferroptosis, with PTGS2 and VCP emerging as potential therapeutic targets.

Context: H-2-168 has pharmacological effects similar to those of harmine, with less toxicity. The health of cells and organisms depends on a delicate balance between mitochondrial fusion and fission.

Objective: This study investigated the roles of H-2-168 and mitochondrial fusion and fission in Echinococcus granulosus.

Materials and methods: Notably, E. granulosus were isolated from fresh sheep livers, and then treated with H-2-168 (25 μg/mL), mitochondrial division inhibitor 1 (Mdivi-1, 25 μg/mL) or the combination of H-2-168:Mdivi-1 (25 μg/mL:12.5 μg/mL). After 24 h of culture, the indices related to E. granulosus were measured. Additionally, Drp1 was knocked down to explore its effects on E. granulosus growth.

Results: The EC₅₀ values of H-2-168, Mdivi-1 and H-2-168:Mdivi-1 against E. granulosus were 44.171, 117.882 and 32.924 μg/mL, respectively. Compared with H-2-168 or Mdivi-1, the combination of H-2-168 and Mdivi-1 showed better inhibitory effects on E. granulosus viability, as well as increased levels of ROS and LDH, decreased ATP levels, inhibited mitochondrial activity and reduced mitochondrial membrane potential (p < 0.05), with the upregulation of Caspase-3, Cyt-c, Drp1, Fis1 and downregulation of Bcl-2, Mfn2 and OPA1. Additionally, Drp1 knockdown was successfully performed in E. granulosus, which significantly inhibited E. granulosus viability (p < 0.05) and further downregulated Mfn2 expression induced by H-2-168.

Discussion and conclusion: Drp1 is closely associated with mitochondrial fusion and fission, and H-2-168 may promote E. granulosus death through disrupting the balance between mitochondrial fusion and fission.

Context: The traditional Japanese medicine Hangeshashinto (HST) is a multicompound drug used for stomatitis. The identification of HST's active ingredients is essential for understanding its mechanism of action and establishing pharmacological quality control markers, but remains unclear due to its multicomponent drug.

Objective: To systematically explore anti-inflammatory ingredients in HST using a combined approach involving a cell-based bioassay and multicomponent analysis, and to identify potential quality marker compounds.

Materials and methods: A cell-based bioassay modeling stomatitis was established using human oral keratinocytes (HOK), with interleukin (IL)-1β-induced prostaglandin E2 (PGE2) as an inflammatory indicator. The PGE2 inhibitory effects of quality-controlled 101 HST manufacturing lots were compared. Multicomponent analysis was performed on the 101 HST samples, correlating the intensity of 121 component peaks with the pharmacological activities. Ingredients with the highest correlation coefficients were validated for their PGE2 inhibitory effects.

Results: A total of 101 HST samples (30 µg/mL: approximately IC₅₀) showed consistent inhibition of IL-1β-induced PGE2 production in HOK (41.33%-67.38% with 100% as IL-1β). Correlation analysis between PGE2 inhibitory activities and peak intensity of 121 components revealed the contribution of each ingredient to the pharmacological effect. Eight ingredients (glycycoumarin, neoglycyrol, [6]-shogaol, [8]-shogaol, [10]-shogaol, [6]-gingerol, [8]-gingerol, and [10]-gingerol) with the highest correlation coefficients (below -0.30) exhibited PGE2-inhibitory potential.

Conclusion: The standardization of current quality control markers contributes to the stability of HST's anti-inflammatory effects. The eight components discovered by this integrated analysis method may become novel quality control marker ingredients for further improving the pharmacological quality of HST.

Context: Natural pigments derived from microbial sources are garnering increasing attention owing to their multifunctional roles in cosmetic and biomedical applications.

Objective: We investigated the antioxidant and biological activities of biocolor extracts of Monascus purpureus cultivated in potato dextrose broth supplemented with 1% Tubtim chumphae (Oryza sativa L., Poaceae) broken rice (MPTR).

Materials and methods: M. purpureus TISTR 3615 pigment yield and quality under fermentation conditions with and without 1% Tubtim chumphae broken rice were examined. Liquid chromatography was performed to determine and quantify the key components of the extracts. The biological activities of the extracts were investigated using antioxidant and enzyme inhibition assays. Cell viability assay was performed to determine the safety of the extracts on human dermal fibroblasts. Furthermore, cellular collagen and elastin production promoted by the extracts was also investigated.

Results: Notably, MPTR extract demonstrated superior pigment production compared with conventional potato dextrose broth cultured fungi. MPTR extract exhibited potent antioxidant properties and was non-cytotoxic to human skin fibroblasts at concentrations up to 0.5 mg/mL. MPTR extract effectively inhibited collagenase and elastase enzymes, and induced cellular collagen type I and elastin production. Moreover, MPTR extract promoted wound healing, significantly reducing the wound area by up to 90% within 48 h.

Discussion and conclusion: MPTR extract from M. purpureus TISTR 3615 fermented with broken rice exhibited antioxidant properties as well as collagenase and elastase inhibitory activities, and promoted cellular collagen type I and elastin production. MPTR extract is a promising skin anti-aging agent for cosmetic and cosmeceutical applications.

Context: Buddleja officinalis Maxim., a prominent medicinal plant from the Scrophulariaceae family, is extensively distributed throught China, Korea, Vietnam, and Myanmar. This phytotherapeutic agent has demonstrated significant clinical efficacy in treating various ophthalmic disorders, such as xerophthalmia, infectious conjunctivitis, keratopathies, corneal ulcerations, and neuropathic ocular pain.

Objective: To explore the potential photoprotective effects of Buddleja officinalis Maxim. extract (BOE) against UVB-induced oxidative damage in human immortalized keratinocytes.

Materials and methods: In this study, we analyzed BOE components using HPLC and evaluated scavenging activities against 2, 2'-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azinobis 3-ethylbenzothiazoline 6-sulfonate (ABTS), and Superoxide anion (O₂^·-) through biochemical assays. Cell viability was assessed with cell counting kit-8 assay (CCK-8) and lactate dehydrogenase (LDH) kits, intracellular reactive oxygen species (ROS) levels were quantified by flow cytometry, and cellular antioxidant enzyme activities were determined using commercial assay kits. To investigate specific antioxidant pathways, qPCR and Western blot analyses were performed.

Results: The biochemical assays demonstrated that BOE possesses significant antioxidant activity. Additionally, BOE significantly alleviated the adverse effects of UVB exposure (30 mJ/cm²), which were characterized by decreased cell viability, elevated LDH activity, increased intracellular ROS levels, reduced activities of superoxide dismutase (SOD), decreased the levels of reduced glutathione (GSH), and increased Malondialdehyde (MDA) content. And the BOE modulates the antioxidant defense pathway by upregulating the mRNA and protein expression levels of nuclear factor erythroid 2-related factor 2(NRF2), heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1).

Discussion and conclusions: Our findings indicate that the photoprotective efficacy of BOE makes it a promising candidate for incorporation as a natural component in pharmaceutical and cosmetic formulations.

Context: Qing-Xin-Jie-Yu Granule (QXJYG) has shown promise in the treatment of myocardial infarction. However, the mechanism of action of QXJYG underlying its anti-inflammation remain unknown.

Objective: The study aimed to evaluate the effectiveness and mechanism of QXJYG in a mouse model of myocardial infarction and hypoxia-induced H9C2 cells.

Materials and methods: Myocardial infarction was induced in mice via left anterior descending coronary artery ligation, and hypoxia-induced H9C2 cells was served as the in vitro model. The cardiac function was evaluated by echocardiography, while myocardial tissue pathology was examined using HE and Masson's trichrome staining. Changes in serum markers of cardiac injury were measured using ELISA kits. The levels of inflammatory cytokines in both the serum and cardiac tissue were quantified using the Bio-Plex Pro Mouse Chemokine assay, and hypoxia-induced inflammatory factors in H9C2 cells were assessed by RT-qPCR. Additionally, western blot analysis was conducted to evaluate the expression of proteins related to the MK2/TTP signaling pathway both in vivo and in vitro experiments.

Results: QXJYG significantly enhanced cardiac function in mice with myocardial infarction, as evidenced by improved myocardial tissue structure, reduced collagen fiber deposition, and lowered serum levels of creatine kinase isoenzyme MB (CK-MB), cardiac Troponin T (cTnT), and brain Natriuretic Peptide (BNP). QXJYG may reduce the expression of inflammatory factors in both the heart and serum of myocardial infarction-induced mice and attenuate hypoxia-induced levels of inflammatory factors in cardiomyocytes by decreasing the ratio of p-MK2/MK2 and increasing the protein expression of TTP.

Discussion and conclusions: QXJYG improved cardiac function and reduced injury, fibrosis, and inflammation after myocardial infarction, likely through modulation of the MK2/TTP signaling pathway.

Context: Chamomile is a widely recognized medicinal herb, and it has been used for its various medicinal properties. Chamomile's widespread recognition and application in medicine highlights its significance in herbal therapeutic practices globally.

Objective: To explore chamomile as a low-risk antimicrobial and anti-inflammatory agent, utilizing clinical characteristics derived from the existing body of evidence from randomized clinical trials within the current literature.

Methods: We conducted a systematic review of randomized clinical trials using the search terms 'chamomile anti-inflammatory antimicrobial randomized clinical trials' and 'chamomile anti-inflammatory antimicrobial'. We sourced data from databases including PubMed, Google Scholar, Cochrane Library, and ClinicalTrials.gov. We then performed a meta-analysis using R to assess the efficacy of chamomile as an anti-inflammatory and an antimicrobial agent, and its impact on mucosal recovery in clinical settings.

Results: A total of 11 randomized clinical trials were identified. The mean difference, confidence intervals, and standard error from the extracted means and standard deviations for relevant outcomes were calculated. Statistical tests from the meta-analysis demonstrated that chamomile exhibited statistically significant reductions in mucositis severity and pain level, indicating the anti-inflammatory effects of chamomile.

Conclusion: This study highlights chamomile's potential as a natural alternative for managing inflammation and microbial infections, offering a promising alternative to standard treatments. Our study suggests chamomile has the potential to act as a natural anti-inflammatory agent. A future study with a larger sample size may provide clinical evidence of this effect.

Systematic review registration number (PROSPERO): CRD42024566615.

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: 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: Physalis peruviana L. (Solanaceae), also known as Poha, has been used in traditional medicine since pre-Columbian times, particularly in treating cancer.

Objective: To study the chemical composition and potential medicinal properties of Poha.

Materials and methods: The fresh fruits and aerial parts of Poha were extracted. The isolation of extract yields a novel withanolide (physaperuvin K; 1) from the edible fruit, and seven withanolides (2-8), including a rare chlorinated withanolide (physalolactone; 2) from the aerial parts. Structure elucidation/determination was performed, some acetate derivatives were prepared (2a-6a), and the compounds were evaluated with in vitro assays indicative of anti-inflammatory activity.

Results: The structure of 1 was elucidated through NMR spectroscopic analyses. The absolute configuration of compound 2 was determined using single-crystal X-ray diffraction. Compounds 1, 2, and 3 exhibited inhibition of tumor necrosis factor-α-induced nuclear factor-kappa B (NF-κB) activity with IC₅₀ values of 10, 60, and 40 nM, respectively, without causing cytotoxicity at a concentration of 50 μM. Furthermore, compounds 1-3 reduced nitric oxide (NO) production in lipopolysaccharide-activated RAW 264.7 mouse macrophage cells with IC₅₀ values ranging from 0.32 to 13.3 μM without overt cytotoxicity. Overall, acetylation did not significantly impact activity, except for compound 4, wherein the IC₅₀ values in the NF-κB and NO assays were reduced from 11.0 to 0.33 μM, and 1.8 to 0.24 μM, respectively.

Conclusions: These findings enhance our understanding of Poha's constituents and potential medicinal properties. One of the most bioactive compounds identified in this study, physaperuvin K, is found in edible fruit.