Frontiers in Pharmacology最新文献

Introduction: Frankincense has demonstrated promising in vitro anticancer activity. However, its conventional delivery methods face significant challenges due to limited oral bioavailability. To address these limitations, this study focuses on developing optimized nanoemulsions (NEs) of Frankincense oil (FO) to enhance its therapeutic efficacy.

Methods: Frankincense resins were extracted and characterized using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), identifying key metabolites including isopinocarveol, α-thujene, p-cymene, carvone, germacrene A, and various methyl esters. FO-based nanoemulsions (FO-NEs) were prepared and optimized using a 3-factor, 3-level Box-Behnken Design (BBD), with 10% FO (v/v), 40% surfactant (cremophor EL), and co-surfactant (Transcutol P). The optimized FO-NEs were evaluated for particle size, polydispersity index (PDI), zeta potential, and morphology using scanning electron microscopy (SEM) and atomic force microscopy (AFM). Cytotoxicity, wound healing, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) assays were performed against breast cancer (MDA-MB-231, MDA-MB-231-TR) and lung cancer (A549, A549-TR, H1299) cell lines.

Results: The optimized FO-NEs exhibited an average particle size of 65.1 ± 4.21 nm, a PDI of 0.258 ± 0.04, and a zeta potential of -22.3 ± 1.2 mV. SEM and AFM confirmed the spherical morphology of the FO-NEs. In vitro cytotoxicity studies revealed enhanced anticancer activity of FO-NEs (IC50 = 13.2 μg/mL) compared to free FO (IC50 = 22.5 μg/mL) against resistant breast cancer MDA-MB-231-TR cells. FO-NEs significantly improved cancer cell internalization, disrupted mitochondrial membrane potential, and increased ROS generation, leading to enhanced cytotoxic effects.

Discussion: The results demonstrate that nanoemulsion-based delivery significantly enhances the bioactivity and cellular uptake of frankincense oil compared to its free form. FO-NEs exhibit potent anticancer activity, particularly against drug-resistant cancer cell lines, suggesting their potential as a viable strategy for improving the therapeutic efficacy of frankincense in cancer treatment.

Background: Xiaoyao San (XYS) has been increasingly used in China for treating chronic fatigue syndrome (CFS), but its efficacy and safety remain unclear.

Objective: To systematically evaluate the efficacy and safety of XYS compared to standard biomedical treatments (SBT) in CFS patients.

Methods: A comprehensive search of English and Chinese databases was conducted up to December 2024. Eligible studies included randomized controlled trials comparing XYS or XYS + SBT to SBT alone. Primary outcomes were effective rate (ER) and fatigue scale-14 (FS-14). Secondary outcomes included self-rating anxiety scale (SAS), self-rating depression scale (SDS), and adverse events (AEs). Data were analyzed using Review Manager 5.4, and evidence quality was assessed using the GRADE approach.

Results: Six studies involving 623 patients were included. The meta-analysis showed that XYS-based interventions significantly improved ER (RR = 1.27, 95% CI: 1.18-1.37, I² = 0%) and FS-14 (MD = 1.77, 95% CI: 1.49-2.06, I² = 54%). Subgroup analyses confirmed consistent efficacy for both XYS vs. SBT and XYS + SBT vs. SBT. Anxiety and depression improved significantly in the XYS + SBT group, with SAS (MD = 5.16, 95% CI: 3.84-6.48, I² = 24%) and SDS (MD = 4.62, 95% CI: 3.15-6.09, I² = 0%). Additionally, the risk of AEs was significantly reduced in the XYS + SBT group compared to SBT alone (RR = 0.48, 95% CI: 0.32-0.72, I² = 0%). However, the quality of evidence was rated "low" due to risk of bias and potential publication bias among the studies.

Conclusion: XYS, whether alone or with SBT, is effective and safe for improving ER, fatigue, anxiety, and depression in CFS patients. However, due to the low quality of the evidence, results should be interpreted cautiously. High-quality RCTs with larger sample sizes and longer follow-up are needed to provide stronger evidence for the clinical use of XYS in managing CFS.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=493084, identifier CRD42023493084.

Introduction: Despite its rarity, cutaneous melanoma (CM) represents the deadliest skin cancer with a high mortality rate, an incidence on the rise, and limited therapeutic options at present. Melanin is a polymeric pigment naturally produced within melanocytes and CM cells that gained a noteworthy attention due to its pharmacological properties, and potential for the design of nanoplatforms with biomedical applications. Up to date, the utilization of melanin-like nanoparticles (MEL-NPs) in cancer treatment has been well-documented, although their efficacy in CM therapy remains scarcely investigated. The current study presents the preclinical evaluation of MEL-NPs as a potential nanomedicine for CM management.

Methods: MEL-NPs were produced through the oxidative polymerization of dopamine and characterized via electron microscopy and UV-VIS spectroscopy. The antioxidant activity was determined by using the DPPH method. The cytotoxic, anti-migratory, anti-clonogenic, pro-oxidant and pro-apoptotic properties of MEL-NPs were investigated in vitro by applying the MTT viability test, bright-field and immunofluorescence microscopy, DCFDA/H2DCFDA test, scratch assay, colony formation assay, and RT-qPCR. The irritant and anti-angiogenic effects were assessed in ovo on the vascularized chorioallantoic membrane (CAM).

Results: The as-made MEL-NPs presented a spherical morphology, an average size of 85.61 nm, a broad UV-VIS absorption spectrum, and a strong antioxidant activity. After a 24 h treatment, MEL-NPs exerted a selective cytotoxicity in SH-4 and B164A5 CM cells compared to HEMa, HaCaT, and JB6 Cl 41-5a healthy skin cells, except for the concentration of 100 µg/mL, at which their viability declined under 70%. Additionally, MEL-NPs accumulated within the intracellular space of CM cells, forming a perinuclear coating, inhibited their motility and clonogenic potential, increased intracellular oxidative stress, targeted the epithelial-to-mesenchymal transition, and induced apoptosis by altering cell morphology, nuclear aspect, F-actin and tubulin distribution, and by modulating the expression of pro- and anti-apoptotic markers. In ovo, MEL-NPs lacked irritant and vascular toxic effects, while exerting an angio-suppressive activity.

Conclusion: MEL-NPs demonstrated promising anti-melanoma properties, showing a selective cytotoxicity, a strong anti-invasive effect and a pro-apoptotic activity in CM cells, while inhibiting CAM angiogenesis, these novel findings contributing to future research on the potential application of this nanoplatform in CM therapy.

Background: Epithelial ovarian cancer (EOC) is a cancer that affects the female reproductive system and is highly lethal. It poses significant challenges in terms of treatment and often has a poor prognosis. In recent years, with the advent of PARPi, the treatment of ovarian cancer has entered a new stage of full-process management. Although more and more drugs have been approved, the therapeutic effect of PARPi is still very limited. With the rapid development of PD-1/PD-L1, CTLA-4, oncolytic viruses, cancer vaccines, adoptive cell therapy, etc., tumor immunotherapy has provided new opportunities for the treatment of ovarian cancer.

Methods: This study used comprehensive transcriptome analysis across multiple databases to gather gene transcripts and clinical features of normal ovarian samples and tissue samples from ovarian cancer. The aim was to explore the mechanisms underlying tumor immunotherapy resistance and to reveal the relationship between ovarian cancer's immune microenvironment and genes linked to inflammation. Various R packages were used for differential gene analysis, enrichment analysis, co-expression network construction, and prognostic model building.

Results: It has been found that the prognosis of ovarian cancer patients is closely associated with sets of genes involved in inflammation. The immune infiltration microenvironment, clinicopathological features, and survival rates differed significantly between two inflammatory gene expression patterns identified using cluster and immune microenvironment analyses. Further analysis revealed that the high-risk group had a higher abundance of M2-type macrophage infiltration, more active anti-tumor immune response, higher tumor stemness score, potentially worse prognosis, and lower response rates to multiple chemotherapy drugs and immune checkpoint inhibitors.

Conclusion: These findings provide new perspectives and potential targets for immunotherapy and prognostic evaluation of ovarian cancer and offer new strategies and directions for clinical treatment and patient management. This study provides crucial information to further our comprehension of drug response mechanisms and tumor immunotherapy. It offers new strategies and methods for the treatment and prognostic improvement of ovarian cancer.

Cardiovascular disease remains the leading cause of mortality, with atrial fibrillation emerging as one of the most common conditions encountered in clinical practice. However, its underlying mechanisms remain poorly understood, prompting ongoing research. Ferroptosis, a recently discovered form of regulated cell death characterized by lipid peroxidation and disrupted cellular redox balance leading to cell death due to iron overload, has attracted significant attention. Since its identification, ferroptosis has been extensively studied in various contexts, including cancer, stroke, myocardial ischemia/reperfusion injury, and heart failure. Growing evidence suggests that ferroptosis may also play a critical role in the onset and progression of atrial fibrillation, though research in this area is still limited. This article provides a concise overview of the potential mechanisms by which ferroptosis may contribute to the pathogenesis of atrial fibrillation.

The COVID-19 pandemic caused by SARS-CoV-2 still lacks effective antiviral drugs. Therefore, a thorough receptor-based virtual screening study was conducted to screen different natural and synthetic drug libraries, such as the Asinex Antiviral, Seaweed Metabolite Database, Medicinal Fungi Secondary Metabolite and Therapeutics Library, and Comprehensive Marine Natural Products Database comprising 6,827, 1,191, 1,830, and 45,000 compounds, respectively, against the main protease enzyme of SARS-CoV-2. Accordingly, three drug molecules (BBB-26580140, BDE-32007849, and LAS-51378804) are highlighted as the best binding molecules to the main protease S1 pocket. The docking binding energy scores of BBB-26580140, BDE-32007849, and LAS-51378804 were -13.02, -13.0, and -12.56 kcal/mol, respectively. Compared to the control Z1741970824 molecule with a binding energy score of -11.59 kcal/mol, the lead structures identified herein showed robust hydrophilic and van der Waals interactions with the enzyme active site residues, such as His41 and Cys145, and achieved highly stable binding modes. The simulations showed a stable structure of the main protease enzyme with the shortlisted leads in the pocket, and the network of binding interactions remained intact during the simulations. The overall molecular mechanics with generalized Born and surface area solvation binding energies of the BBB-26580140, BDE-32007849, LAS-51378804, and control molecules are -53.02, -56.85, -55.44, and -48.91 kcal/mol, respectively. Similarly, the net molecular mechanics Poisson-Boltzmann surface area binding energies of BBB-26580140, BDE-32007849, LAS-51378804, and control are -53.6, -57.61, -54.41, and -50.09 kcal/mol, respectively. The binding entropy energies of these systems showed lower free energies, indicating their stable nature. Furthermore, the binding energies were revalidated using the water swap method that considers the role of the water molecules in bridging the ligands to the enzyme active site residues. The compounds also revealed good ADMET properties and followed all major rules of drug-likeness. Thus, these compounds are predicted as promising leads and can be subjected to further experimental studies for evaluation of their biological activities.

The SOX9 gene locus is not only extensive but also intricate, and it could promote fibrosis in different organs or tissues, including cardiac fibrosis, liver fibrosis, kidney fibrosis, pulmonary fibrosis, as well as other organ fibrosis. Many disorders are associated with the process of fibrosis; moreover, fibrosis is a common symptom of chronic inflammatory diseases, characterized by the accumulation of excessive components in the extracellular matrix through different signaling pathways. The advanced stage of the fibrotic process leads to organ dysfunction and, ultimately, death. In this review, we first give an overview of the original structure and functions of SOX9. Second, we will discuss the role of SOX9 in fibrosis in various organs or tissues. Third, we describe and reveal the possibility of SOX9 as an antifibrotic treatment target. Finally, we will focus on the application of novel technologies for SOX9 and the subsequent investigation of fibrosis.

Aortic dissection (AD) is a life-threatening vascular condition marked by the separation or tearing of the aortic media. Ferroptosis, a form of iron-dependent programmed cell death, occurs alongside lipid peroxidation and the accumulation of reactive oxygen species (ROS). The relationship between ferroptosis and AD lies in its damaging effect on vascular cells. In AD, ferroptosis worsens the damage to vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), thereby weakening the vascular wall's structural integrity and accelerating the onset and progression of the condition. However, the molecular mechanisms through which ferroptosis regulates the onset and progression of AD remain poorly understood. This article explores the relationship between ferroptosis and AD.

Interstitial cystitis is a fierce syndrome affecting the quality of life of thousands of individuals around the globe. It causes immense pain in the bladder and associated viscera along with inflammation-like lesions. The current medicinal and pharmacological research focuses on the protective and curative effects of phytochemicals in several ailments. Phytochemicals derived from many medicinal plants have shown potent outcomes in protection against various pathological conditions including interstitial cystitis. This review has summarized the insights of in vitro and in vivo studies regarding the effects of phytochemicals in fading the inflammation in bladder tissue and exhibiting a protective effect on the urothelium. Hemorrhagic cystitis is a common manifestation in patients undergoing chemotherapy with cyclophosphamide and related alkylating agents. Sodium 2-mercaptoethane sulfonate (Mesna) has traditionally been employed in clinical practice to counter cyclophosphamide-induced cystitis in humans. However, cyclophosphamide has been employed in developing animal models of interstitial cystitis in in vivo studies. Phytochemicals including quercetin, beta-caryophyllene, curcumol, boswellic acid, caftaric acid, some flavonoids and other secondary metabolites being a consequential component of numerous medicinal plants, have displayed a significant reduction in the levels of proinflammatory cytokines including TNF-α, NFĸB, IL-1β, NLRP3 inflammasome, IL-6, IL-2, matrix metalloproteinases etc. Uroprotective outcomes of these phytochemicals have been found to result in diminished oxidative stress and restoration of glutathione, superoxide dismutase, and related proteins in the inflamed bladder tissue. Many in vivo studies involving cyclophosphamide-induced interstitial cystitis have confirmed these findings. The coupling of phytotherapy with novel drug delivery systems such as nanoparticles, liposomes, nanotubes, quantum dots, etc. can help translate these beneficial effects of phytochemicals into clinical practice. Further investigations of these phytochemicals can provide intuition regarding the development of newer drug molecules having exclusive activity for attenuating interstitial cystitis.

Purslane (Portulaca oleracea L.) with heat-clearing and detoxicating, anti-inflammatory and resolving swelling, relieving itching and astringing function, has remarkable efficacy for acute eczema. However, most of the clinical applications of purslane are freshly prepared decoction, not as easy to apply as cream, because the decoction is easy to breed bacteria and easy to oxidize. Here, based on the theory of Chinese medicines compatibility, we made a purslane-tannic acid hydrogel (PL-HATA) by simple methods under mild conditions to solve the drawbacks of easy oxidation and inconvenience of use of Purslane. The antimicrobial activity of PL-HATA hydrogel can exert an excellent antimicrobial effect, reducing the flora on the skin of acute eczema and further relieving the symptoms of acute eczema. At the same time, it creates a normal reactive oxygen species (ROS) microenvironment for acute eczema and promotes recovery from acute eczema. It also improves the symptoms of acute eczema by promoting cell proliferation and migration. Importantly, it resulted in improved skin lesion scores, scratching behavior, eosinophil infiltration, swelling and inflammation levels, immune homeostasis, and histopathological changes in rats with acute eczema. Besides, HATA hydrogel is not only suitable for Purslane's decocted metabolites but also for Purslane's freshly squeezed metabolites. This purslane application protocol solved the drawbacks of Purslane's decoction, improved its storage stability and convenience of use, which is the key issue to further promote its clinical application.