Pharmaceutical Biology最新文献

Context: Use of botanicals is increasing. While often considered as safe, neuromodulatory effects have been demonstrated previously.

Objective: Establish the neuroactive potential of 13 botanical extracts. For 8 of these, we made a direct comparison with their major constituent.

Materials and methods: We used microelectrode array (MEA) recordings of primary rat cortical cultures to evaluate dose-response relationships on neuronal network function in vitro.

Results: Exposure to extracts from milk thistle, usnea, green tea, aristolochia, and ephedra mildly inhibited neuronal activity with distinct neuronal activity phenotypes. Extracts of tripterygium, yohimbe, kratom, and kava strongly inhibited neuronal activity. Despite differences in the degree of inhibition, all inhibitory extracts show No Observed Effect Levels (NOELs) of 1-5 µg/mL. Exposure to aconite, blue cohosh, goldenseal and oleander induced specific activity phenotypes characterized by hyperexcitation and/or intensification of (network) burst activity. While the extracts exhibit a narrow effective dose range, the extracts from aconite, goldenseal and oleander are most potent with NOELs of 0.25-0.5 µg/mL.

Silybin B (milk thistle), epigallocatechin gallate (green tea), yohimbine (yohimbe), dihydrokavain (kava), mitragynine (kratom), aconitine (aconite), berberine (goldenseal) and oleandrin (oleander) were tested to investigate if the distinct neuronal activity phenotypes, indicative for the presence of multiple modes of action, are due to the known bioactive constituents of the extracts. For most constituents the activity phenotype is comparable to the extract, although the extract generally has a higher potency.

Discussion and conclusion: Botanical extracts and constituents evoke diverse activity phenotypes, highlighting the complexity of hazard characterization of botanicals.

Context: The skin is the largest organ of the body, and its proper care significantly influences the well-being of the entire organism. Therefore, the ingredients of cosmetics and dermocosmetics should inhibit processes leading to inflammation and degradation of skin macromolecules.

Objective: To select the most promising Rubus caesius L. extract for use in cosmetic and dermocosmetic applications.

Materials and methods: Water and ethanol extracts from leaves and stems of Rubus caesius L. (European dewberry, Rosaceae) were tested for their antioxidant properties, protective effects against pathogenic bacterial strains and the influence on tyrosinase and collagenase activity. The most biologically active extracts were selected and analyzed using the HPLC method to estimate the content of major phenolic acids and their ability to penetrate into and through porcine skin from hydrogels.

Results: Ethanol extracts from Rubus caesius L. demonstrated significant biological activity, particularly in scavenging the ABTS radical and inhibiting tyrosinase and collagenase activity. Furthermore, ethanol extracts were effective against pathogenic bacteria, but not against commensal skin microbiota. Ethanol extracts from leaves and stems were rich in phenolic acids. The permeation experiment through porcine skin from hydrogels revealed that gallic acid and neochlorogenic acid from ethanol leaves extract exhibited the highest permeation capability.

Discussion and conclusion: The ethanol extract demonstrated substantial activity in protecting the skin against pathogens, oxidative stress, and macromolecular degradation. The presence and transdermal permeability of phenolic acids were also confirmed. These findings highlight the high potential of Rubus caesius leaf ethanol extract for inclusion in cosmetic and dermocosmetic formulations.

Context: Sophoridine, an alkaloid quinolizidine derived from Sophora flavescens Aiton (Fabaceae), has strong anti-tumor activity in a variety of malignancies. Nevertheless, the effects and underlying mechanism of sophoridine on breast cancer are not fully understood.

Objective: To identify the key targets and potential pharmacological mechanisms of sophoridine against breast cancer.

Materials and methods: MCF-10A, MCF-7 and MDA-MB-231 cells were treated with sophoridine for 24 or 48 h. MTT, colony formation assay, flow cytometry, wound healing, and Transwell assay were employed to illustrate the anti-tumor effects of sophoridine on breast cancer. Network pharmacology and molecular docking were used to determine the targets for sophoridine in breast cancer, and confirmed by molecular dynamics simulation and CETSA-western blot assay. Additionally, the functional rescue and signaling pathway regulated by sophoridine was analyzed.

Results: Sophoridine suppressed the proliferation, migration, and invasion of breast cancer cells. The IC₅₀ value of sophoridine for 48 h in MCF-10A, MCF-7 and MDA-MB-231 was 363 μM, 87.96 μM and 81.07 μM, respectively. PIM1 was the key target for sophoridine in breast cancer. Furthermore, PIM1 overexpression significantly reversed the suppressive impacts of sophoridine on growth and migration in breast cancer cells. Mechanistically, sophoridine inhibited the phosphorylation of ASK1 and activated JNK/p38 MAPK signaling pathway by downregulating PIM1 expression, and thus exhibited anti-tumor effects.

Discussion and conclusion: Taken together, sophoridine relies on targeting PIM1 to inhibit cell proliferation and migration in breast cancer, which might be related to the activation of ASK1/MAPK axis, suggesting the therapeutic potential of sophoridine for breast cancer.

Context: Genistein, a soy-derived isoflavone, exhibits structural similarities with 17β-estradiol and demonstrates antioxidant, anti-inflammatory, and estrogenic properties. Despite its low bioavailability limiting its clinical application, it shows potential for breast cancer prevention and treatment.

Objective: This review aims to summarize the pharmacological effects and molecular mechanisms of genistein in breast cancer, focusing on its therapeutic potential, strategies to overcome bioavailability limitations, and its role in personalized medicine. Differential impacts among population subgroups are also discussed.

Methods: A systematic review was conducted using PubMed, ScienceDirect, and Google Scholar databases. Studies were selected based on their focus on genistein's mechanisms of action, strategies to enhance its bioavailability, and interactions with other therapies.

Results: Genistein exerted anticancer effects by modulating estrogen receptor β (ERβ), inhibiting angiogenesis, arresting the cell cycle, and inducing apoptosis. Its antioxidant properties help mitigate tumor-associated oxidative stress. Bioavailability enhancement strategies, such as nanoparticle and lipid-based formulations, show promise. Age-dependent effects were evident, with distinct responses observed in prepubertal, menopausal, and postmenopausal populations, underscoring its potential for personalized therapies. Furthermore, genistein influences epigenetic modifications, including DNA methylation and miRNA expression, bolstering its anticancer efficacy.

Conclusion: Genistein is a promising candidate for breast cancer therapy, particularly for personalized treatment. Strategies to enhance bioavailability and further clinical research are essential to optimize its therapeutic potential and evaluate its efficacy in combination therapies.

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.