Search Results (134)

Background: Glioblastoma multiforme (GBM) is an aggressive primary brain malignancy associated with poor prognosis and limited therapeutic options. Nanoparticle-based drug delivery systems provide a promising strategy to enhance treatment efficacy by circumventing barriers such as the blood–brain barrier. This study was conducted to synthesize, characterize, and evaluate the in vitro anticancer potential of andrographolide–iron oxide nanoparticles (AG-IONPs) against GBM cells. Methods: Iron oxide nanoparticles (IONPs) were synthesized through co-precipitation and subsequently functionalized with andrographolide. Morphology, size, and surface charge were assessed by transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis. Functionalization was confirmed by Fourier-transform infrared spectroscopy (FTIR) and UV–Vis spectroscopy. Nanoparticle stability was monitored over three months. Cytotoxicity toward DBTRG-05MG cells was evaluated using MTT assays at 24, 48, and 72 h, while anti-migratory effects were determined using scratch-wound assays. Results: TEM analysis revealed nearly spherical IONPs (7.0 ± 0.15 nm) and AG-IONPs (13.5 ± 1.25 nm). DLS indicated an increased hydrodynamic diameter following functionalization, while zeta potential values decreased from +21.22 ± 1.58 mV to +8.68 ± 0.87 mV. The successful incorporation of andrographolide was confirmed by FTIR and UV–Vis spectra. AG-IONPs demonstrated excellent colloidal stability for up to three months. Cytotoxicity assays revealed a dose- and time-dependent decrease in cell viability, with LC₅₀ values declining from 44.01 ± 3.23 μM (24 h) to 15.82 ± 2.30 μM (72 h). Scratch-wound assays further showed significant inhibition of cell migration relative to untreated controls. Conclusions: AG-IONPs exhibit favorable physicochemical properties, long-term stability, and potent anti-proliferative and anti-migratory effects against GBM cells in vitro. These findings support their potential as a multifunctional therapeutic platform, warranting further preclinical investigation. Full article

Andrographolide (ADG) is a typical poorly water-soluble drug, and a co-amorphous strategy was used here to improve its aqueous solubility. Co-amorphous systems of ADG and amino acids with a 1:1 molar ratio were screened via the neat ball milling method. L-lysine (Lys) and L-tryptophan (Trp) can be used as co-formers with ADG, forming a co-amorphous phase, which was confirmed by powder X-ray diffraction, IR and Raman spectroscopy. ADG-Trp showed poor solubility at 37 °C, which was close to that of raw ADG (0.08 mg·mL⁻¹). ADG-Lys showed unexpectedly enhanced solubility, at 0.5 mg·mL⁻¹ in the media of water and PBS (pH 7.4) and 0.3 mg·mL⁻¹ in the medium of HCl buffer (pH 1.2) at 37 °C. ADG-Lys showed good storage stability for 5 months, but its thermal stability was poor and it could recrystallize at 100 °C. Compared with ADG-Trp, ADG-Lys has weaker hydrogen bonding interactions and stronger hydrophobic interactions related to ADG molecules, which might cause the unusual enhancement in solubility. To our knowledge, ADG-Lys prepared in this work shows the maximum ADG content (70 wt.%) and the highest ADG solubility among the reported ADG amorphous solid dispersions and co-amorphous systems. Full article

The increasing demand for sustainable disease management in aquaculture has intensified interest in plant-based therapeutics. This study evaluated the formulation and efficacy of andrographolide-loaded nanostructured lipid carriers (AND-NLCs) in Nile tilapia (Oreochromis niloticus) challenged with Streptococcus agalactiae ENC06. AND-NLCs were prepared by the phase-inversion technique and characterized by dynamic light scattering, transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and in vitro release profiling. Antibacterial activity was assessed by measuring inhibition zone diameters, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). Growth performance, feed utilization, hepatosomatic index (HSI), and disease resistance were evaluated over a 60-day feeding trial. The AND-NLCs exhibited an optimal particle size (189.6 nm), high encapsulation efficiency (90.58%), sustained release, and structural stability. Compared to the free AND and control group, AND-NLC supplementation significantly improved growth, feed efficiency, HSI, and positive allometric growth. It also enhanced survival (73.3%) and relative percent survival (RPS = 65.6%) following S. agalactiae ENC06 infection. Antibacterial efficacy and physiological responses showed positive correlations with nanoparticle characteristics. These findings suggest that AND-NLCs enhance bioavailability and therapeutic efficacy, supporting their potential as a functional dietary additive to promote growth and improve disease resistance in tilapia aquaculture. Full article

Background: Natural products play a crucial role in cancer treatment due to their ability to selectively target cancer cells. Andrographolide, a major constituent of Andrographis paniculata, exhibits potential anticancer properties. Considering the pharmacological importance of nitrogen-based heteroaromatic scaffolds, particularly pyrazole motifs, this study aimed to integrate the pyrazole pharmacophore with the andrographolide scaffold to develop novel therapeutic candidates. Methods: Twenty novel 3,19-(N-phenyl-3-aryl-pyrazole) acetals of andrographolide and isoandrographolide were synthesized and characterized using UV-Vis, FT-IR, NMR, and HRMS. Initial anticancer screening was conducted by the National Cancer Institute (NCI), USA, against 60 human cancer cell lines. The most promising compound, 1f (R = 4-F), was selected for further biological evaluation in the MDA-MB-231 breast cancer cell line. Results: The MTT assay results demonstrated that compound 1f exhibited strong, dose-dependent anti-proliferative effects. The apoptosis analysis of 1f revealed a time-dependent increase in apoptotic cells, and cell cycle studies indicated S phase arrest in MDA-MB-231 cells. Antioxidant activity via the DPPH assay identified compounds 1b (R = 3-NO₂) and 2b (R = 3-NO₂) as the most effective radical scavengers. The most active compounds were also evaluated for drug-likeness using in silico Lipinski’s rule assessments. Conclusions: The synthesized 3,19-(N-phenyl-3-aryl-pyrazole) acetals of andrographolide and isoandrographolide exhibited promising anticancer and antioxidant properties. Among them, compound 1f showed the most significant activity, supporting its potential as a lead candidate for further anticancer drug development. Full article

Andrographolide (AP), a bioactive compound from Andrographis paniculata, is known for its anti-inflammatory and antioxidant properties, both essential for wound healing. However, its effects on energy metabolism during tissue repair and its role in UVB-induced photoaging remain poorly understood. This study explored AP’s multitarget therapeutic effects on wound healing under photoaging conditions (PhA/WH) using network pharmacology and experimental validation. Scratch wound assays showed that AP promoted keratinocyte migration in UVB-exposed HaCaT cells. Bioinformatic analysis identified 10 key targets in PhA/WH, including TNF-α, IL-1β, JUN, PPARγ, MAPK3, TP53, TGFB1, HIF-1α, PTGS2, and CTNNB1. AP suppressed UVB-induced pro-inflammatory gene expression (IL-1β, IL-6, IL-8, and COX-2) and inhibited the phosphorylation of ERK1/2 and P38, while enhancing Hypoxia-Inducible Factor-1alpha (HIF-1α) and peroxisome proliferator-activated receptors (PPARγ) expression. GC/MS-based metabolomics revealed that AP reversed UVB-induced disruptions in fatty acid metabolism, glycolysis/gluconeogenesis, and tricarboxylic acid (TCA) cycle, indicating its role in restoring the metabolic balance necessary for tissue regeneration. In conclusion, andrographolide modulates key inflammatory and metabolic pathways involved in wound repair and photoaging. These mechanistic insights contribute to a better understanding of the molecular processes underlying skin regeneration under photodamage and may inform future therapeutic strategies. Full article

This study explores the viral dynamics of SARS-CoV-2 infection within host cells by incorporating the pharmacological effects of andrographolide—a bioactive compound extracted from Andrographis paniculata, renowned for its antiviral, anti-inflammatory, and immunomodulatory properties. Through the application of mathematical modeling, the interactions among the virus, host cells, and immune responses are simulated to provide a comprehensive analysis of viral behavior over time. Two distinct models were employed to assess the impact of varying andrographolide dosages on viral load, target cell populations, and immune responses. One model revealed a clear dose–response relationship, whereas the other indicated that additional biological or pharmacological factors may modulate drug efficacy. Both models demonstrated stability, with basic reproductive numbers (R₀) suggesting the potential for viral propagation in the absence of effective therapeutic interventions. This study emphasizes the significance of understanding the pharmacokinetics (PK) and pharmacodynamics (PD) of andrographolide to optimize its therapeutic potential. The findings also underscore the necessity for further investigation into the compound’s absorption, distribution, metabolism, and excretion (ADME) characteristics, as well as its prospective applications in the treatment of not only COVID-19 but also other viral infections. Overall, the results lay a foundational framework for future experimental research and clinical trials aimed at refining andrographolide dosing regimens and improving patient outcomes. Full article

Andrographolide, fucoidan, or a combination of both compounds were evaluated to determine their effects on the antiviral response in the Atlantic salmon macrophage-like cell line (SHK-1) infected with infectious pancreatic necrosis virus (IPNV). We assessed the transcript expression levels of key molecules involved in the interferon (IFN)-dependent antiviral response, as well as the viral load in cells treated with these compounds. In non-infected cells, incubation with either fucoidan, andrographolide, or a mixture of both resulted in an increase in the transcript expression of IFNα1 and various interferon-stimulated genes (ISGs). In IPNV-infected cells, treatment with either fucoidan or andrographolide separately did not significantly enhance the antiviral response compared to that of infected cells that had not previously been treated with these compounds. In contrast, the combination of andrographolide and fucoidan led to a marked increase in the transcript expression of viperin and a significant reduction in viral load. Overall, combining andrographolide and fucoidan resulted in a greater reduction in IPNV viral load in infected cells than that noted when the compounds were administered individually. Our findings suggest that pre-incubation with this mixture promotes the establishment of a protective antiviral state against IPNV, likely mediated by an IFN-dependent response. Full article

Background/Objectives: The search for new anticancer agents from natural sources remains a key strategy in drug discovery. This study aimed to synthesize and evaluate novel triazole derivatives of the diterpenic lactone andrographolide for their antiproliferative activity against various cancer cell lines. Methods: Twenty-two new triazole derivatives (5–26), of the triacetyl derivative (2) of the diterpenic lactone andrographolide (1), were synthesized via the azide-alkyne “click reaction”. The antiproliferative effects of compounds 1–26 were evaluated using the sulforhodamine B assay against a panel of cancer cell lines and a non-tumorigenic colon cell line. A representative compound, triazole derivative 12, was further evaluated in human pancreatic ductal adenocarcinoma (PANC-1) cells for its effects on the cell cycle, apoptosis, migration, and drug synergy with 5-fluorouracil. Results: Several compounds, specifically, 9, 14, 16, and 17, bearing a phenyl moiety, exhibited improved antiproliferative activity compared to the parental compound 1. Derivative 12, selected for further investigation, induced G2/M cell cycle arrest and apoptosis in a concentration-dependent manner. Additionally, this compound significantly reduced cell migration and demonstrated synergistic effects with 5-fluorouracil in PANC-1 cells. Conclusions: The synthesized andrographolide-based triazole derivatives, particularly compound 12, showed promising antiproliferative activity and mechanisms relevant to cancer therapy. These findings support their potential as lead compounds for further development in anticancer research. Full article

Terpenoids have significant biological activity and good clinical efficacy and are important for defence and physiological regulation in plants. Andrographolide and similar labdane-related diterpenoids have been isolated and characterized as the main medicinal constituents of drugs from Andrographis paniculata. To better study the diversity of terpenoids of A. paniculata, a total of 39 ApTPSs were screened, and 27 full-length genes encoding ApTPSs were obtained. The results showed that ApTPS4 could convert GGPP to ent-CPP and that ApTPS5 could convert ent-CPP to kaurene. This study first identified six sesquiterpene synthases with biological activity and also indicated the presence of sesquiterpenes with multiple skeletons in A. paniculata. The increase in the number of ent-copalyl diphosphate synthases and the loss of biological function by most sesquiterpene synthases and monoterpene synthases may explain why diterpenoids are the main specific metabolites in A. paniculata compared with the metabolites produced by AtTPSs found in the Arabidopsis thaliana genome. As revealed by site-directed mutagenesis, 533Val of ApTPS16 is an important site for maintaining the single main product capability, and 534Tyr of ApTPS17 may also be more important. The ApTPS17 Y534V mutation caused it to lose its main biological function. This study characterized a novel ent-copalyl diphosphate synthase and six sesquiterpene synthases. This provided evidence for the existence of other terpenoids and revealed the diversity of chemical components, providing a reference for future pharmacological research for A. paniculata. Full article

This study examined the degree of monomer conversion (DC) and mechanical properties of experimental orthodontic adhesives containing monocalcium phosphate monohydrate (MCPM), Sr-bioactive glass (Sr-BAG) nanoparticles, and andrographolide. Experimental adhesives were prepared with a 4:1 powder-to-liquid ratio, containing methacrylate monomers with varying formulations of glass fillers and additives. DC was measured using ATR-FTIR (n = 5) with and without bracket placement under two curing protocols: conventional LED (1200 mW/cm², 20 s) and high-intensity LED (3200 mW/cm², 3 s). The biaxial flexural strength and modulus were tested after 4-week water immersion (n = 8). Transbond XT was used as the commercial comparison. Transbond XT exhibited higher DC (33–38%) than the experimental materials. Conventional LED curing produced higher DC than high-intensity LED, while bracket placement reduced DC by approximately 10% in the experimental materials but minimally affected Transbond XT. Transbond XT demonstrated a superior biaxial flexural strength (188 MPa) compared to the experimental adhesives (106–166 MPa, p < 0.05). However, the experimental formulations with low additive concentrations showed a comparable biaxial flexural modulus (5.0–5.5 GPa) to Transbond XT (5.6 GPa) (p > 0.05). Although the experimental adhesives exhibited lower DC and strength than the commercial product, their values still met the ISO standards, suggesting their potential clinical viability despite their modified compositions. Full article

Retinol is well-known anti-aging material in the cosmetics industry, owing to its proven superior efficacy both in vitro and in vivo. Despite its high efficacy, retinol is associated with limitations, such as skin irritation and its potential photodegradation. Retinol is converted into retinoid acid within cells, which then exerts a cellular response by activating both the retinoic acid receptor (RAR) and retinoid x receptor (RXR). Noting that RAR activity is associated with skin irritation and RXR activation alone can enhance skin-related indicators without inducing inflammation, we developed an alternative approach for skin anti-aging focusing solely on RXR activation. We found that combined treatment of andrographolide and Bidens pilosa extract successfully activated RXR alpha and enhanced RXRA gene expression. Moreover, we investigated their efficacy using dermal fibroblasts and keratinocytes and found that they enhanced the gene expression of extracellular matrix (ECM) proteins with anti-oxidant and anti-inflammation efficacies. Finally, in a human clinical trial, we confirmed that our materials successfully improved wrinkles in various areas, skin elasticity and hydration without causing irritating side effects. These findings highlight the potential of our RXR alpha-activating materials as an anti-wrinkle solution that avoids the typical side effects associated with retinol. Full article

Andrographis paniculata is a plant of the Acanthaceae family and its primary bioactive constituent, andrographolide, exhibits a broad spectrum of pharmacological activities and notable clinical efficacy. However, its poor solubility and limited bioavailability pose significant challenges for therapeutic applications. To overcome these limitations, researchers have synthesized andrographolide sulfonates by reacting andrographolide with ethanol and sulfuric acid. This sulfonated derivative significantly enhances water solubility and bioavailability while retaining key pharmacological properties such as anti-inflammatory and antiviral activities. As a representative formulation, Xiyanping injection has been widely employed in the treatment of respiratory infections, pneumonia, and related conditions, playing a critical role during the COVID-19 pandemic. Despite its widespread application, there has yet to be a comprehensive review of its chemical composition and pharmacological mechanisms. Additionally, the safety of Xiyanping injection remains a topic of some debate. This review systematically examines the chemical composition, pharmacological activities, clinical applications, and adverse reactions of andrographolide sulfonates and their formulation in Xiyanping injection to provide a scientific basis for further research and applications, while also offering valuable insights for the development of similar sulfonated drugs. Full article

Andrographis paniculata is mainly used to treat skin inflammations, wounds, and infections. In this study, Andrographis Herba, the aerial part of the plant, was proven to increase the viability of UVB-damaged HaCat cells and reduce reactive oxygen species levels. The chemical composition of Andrographis Herba extract (AHE) was analyzed using UPLC-Q-TOF-MS, and diterpene lactones were identified as its primary constituents. Then, the fraction of diterpene lactones was prepared and exhibited similar effects to AHE. AHE, its diterpene lactones component, and its representative constituent andrographolide all decreased the expression of IL-1β, IL-6, and CDKN1A. Furthermore, the protective effects of AHE and its active ingredients on UVB-damaged epidermal stem cells were investigated. Notably, the combined treatment with andrographolide and collagen XVII enhanced the viability of UVB-damaged epidermal stem cells, increased the expression of stemness markers integrin β1 and p63, and decreased the expression of the differentiation marker keratin 10. This combination demonstrated significant synergy in maintaining skin homeostasis, which provides evidences for the development of skin-protective products. Full article

In this manuscript, the effects of two extracts from Andrographis paniculata were tested: (a) an extract titrated to 49.7% of andrographolide and obtained from leaves of the plant: (b) the pure andrographolide titrated to 99%. The extracts were dissolved in 1-butanol and tested on tumor lines (MCF7 and SH-SY5Y) and the non-tumor line (Huvec) to understand the effects on cell proliferation. The addition of a sonication process improved their dissolution and efficacy making these extracts unique and innovative. The experiments conducted (viability measurements, solubility of the extracts, IC₅₀ tests, measurement of oxidative potential, lipid and cytosolic calcium concentration, and mortality assessment by annexin assay) showed a different behavior of the extracts on cancer cells and not. In particular, the extracts did not cause toxic effects on the viability of the Huvec cells, while both tumor lines were damaged, demonstrating that cancer cells are more susceptible to extracts of A. paniculata than healthy cells. The mechanism of action responsible for the damage detected involved the functioning of the endoplasmic reticulum organelle and finally resulted in apoptotic death. For this reason, the extracts considered have shown a potential anti-tumor role and A. paniculata could be used and exploited in pharmacological therapy against cancer. However, further studies, obtained in clinical practice, should be conducted to increase knowledge of the effects of A. paniculata on the organism and its phytotherapeutic role. Full article