Search Results (126)

Light spectrum is a crucial environmental factor influencing plant growth and secondary metabolite production in controlled-environment agriculture. This study investigated the combined effects of light spectral composition on growth performance and andrographolide accumulation in Andrographis paniculata (Burm.f.) cultivated in a plant factory system. Two Thai cultivars, RBR and TTT, were grown under white light and various red–green–blue (R:G:B) LED ratios during the vegetative and flowering stages. Plant morphological traits, biomass accumulation, and andrographolide derivatives (AP1, AP4, AP6, and total AP) were quantified. Growth and biomass production were significantly enhanced under white light and red-enriched spectra, particularly during the vegetative stage, whereas stem elongation exhibited reduced sensitivity to light spectral quality during the flowering stage. In contrast, andrographolide accumulation showed a strong cultivar-dependent response to light spectrum. The TTT cultivar showed pronounced increases in AP1, AP4, AP6, and total AP under blue-enriched spectra, with the 60B:10G:30R treatment producing the highest total diterpenoid content in both cultivars, while the RBR cultivar displayed limited responsiveness to spectral variation. These results demonstrate light spectrum affecting both biomass production and phytochemical accumulation. Optimization of light spectral composition combined with appropriate cultivar selection offers an effective strategy for enhancing pharmaceutical-grade andrographolide production in plant factory systems. Full article

This study presents an Internet of Things (IoT)-assisted semi-open hydroponic system for cultivating Andrographis paniculata under tropical conditions, aiming to enhance biomass productivity, andrographolide (AG) yield, and production efficiency. IoT-assisted hydroponics, non-IoT hydroponics, and soil-based cultivation were compared in 10 m² greenhouses. The IoT system enabled real-time monitoring and adaptive regulation of temperature, relative humidity, light intensity, nutrient solution pH, and electrical conductivity (EC). IoT-assisted hydroponics achieved earlier harvest (≈90 days) and the highest fresh biomass yield (0.409 ± 0.014 kg m⁻²) while maintaining per-plant productivity (15.74 ± 0.54 g plant⁻¹) comparable to soil-based cultivation. Andrographolide concentration reached 25.58 ± 3.36 mg g⁻¹ DW (2.56% w/w), meeting pharmacopeial requirements. Owing to stable environmental regulation and tolerance to high planting density, the IoT system produced the highest areal AG productivity (209.5 mg m⁻²), representing a four- to tenfold increase over the other systems. Despite higher operational costs, IoT-assisted hydroponics achieved the lowest AG unit cost (≈6.77 USD g⁻¹). While most previous studies emphasize tissue-level AG concentration, system-level productivity and cost efficiency under realistic cultivation conditions remain insufficiently explored. Overall, IoT-enabled semi-open hydroponics provides a scalable and economically viable approach for medicinal plant production, bridging the gap between open-field cultivation and fully controlled plant factory systems. Full article

Background/Objectives: Astrocytes are key regulators of brain energy homeostasis, integrating glucose metabolism with antioxidant support for neuronal function. Dysregulation of these processes contributes to neurodegenerative diseases, including Alzheimer’s disease. Andrographolide, a bioactive diterpenoid from Andrographis paniculata, has been reported to exert neuroprotective effects through the modulation of Wnt/β–catenin signaling and neuronal metabolism; however, its actions on astrocytic metabolic pathways remain insufficiently characterized. Methods: Here, we investigated the effects of andrographolide on metabolic and redox parameters in primary mouse cortical astrocytes. Results: Andrographolide increased glucose uptake and antioxidant capacity without affecting AMPK activation or the activity of core glycolytic enzymes. Instead, it selectively enhanced glucose-6-phosphate dehydrogenase activity, promoting glucose flux through the pentose phosphate pathway in a partially Wnt-dependent manner. This metabolic reprogramming was associated with increased NADPH availability and glutathione levels, together with a reduced ATP/ADP ratio, consistent with a shift toward redox maintenance rather than maximal energy production. Conclusions: Collectively, these findings highlight astrocytic metabolic plasticity as a relevant and underexplored target of andrographolide and support the concept that natural compounds can enhance brain resilience by modulating glial redox metabolism. Full article

Objectives: This study aimed to assess the intestinal permeation behaviors of andrographolide (AG) and 14-deoxy-11,12-didehydroandrographolide (DDAG), diterpene lactones from Andrographis paniculata extract (APE), pure AG, and three distinct source APEs. The effects of different solvents were also investigated. Methods: Solubility investigation was performed using APE. APEs and pure AG were prepared as liqui-masses, cohesive mixtures of APE, solvents, and solid carriers. PXRD, in vitro release, and ex vivo intestinal permeation using the non-everted gut sac method were investigated. Results: Solubility of AG and DDAG in N-methyl-2-pyrrolidone (NMP) > NMP/diethylene glycol monoethyl ether (DG) mixtures > DG. PXRD indicated that crystallinity loss of liqui-mass was affected by solvent’s solvency capacity. The release behaviors of AG and DDAG in phosphate buffer from pure AG and APEs varied depending on their solid state. The release efficiencies of AG and DDAG from liqui-mass systems increased significantly. The apparent permeability (P_app) of AG from pure AG was 0.11 ± 0.05 ×10⁻⁵ cm·s⁻¹, which was 11–25 times less than that of APEs. The P_app of DDAG from various APEs was comparable, ranging between 5.95 and 7.37 × 10⁻⁵ cm·s⁻¹. The presence of a solvent, specifically NMP, in liqui-mass significantly enhanced the release rate and permeation flux. The P_app of AG and DDAG from liqui-mass increased by factors of 1.0–2.3 and 1.1–2.7, respectively. Conclusions: This study is the first to emphasize the differences in the release and intestinal permeation characteristics of AG and DDAG from APEs. These findings offer essential insights into the intestinal permeation behavior of diterpene lactones, along with a straightforward mechanistic strategy for enhancement. Full article

Background: Prostate cancer remains a major contributor to cancer-related morbidity and mortality worldwide, emphasizing the need for safer and more effective therapeutic options. Andrographolide, a diterpenoid lactone derived from Andrographis paniculata, has shown promising anticancer activity, yet its effects on microRNA (miRNA) regulation in prostate cancer remain insufficiently explored. Methods: In this study, we evaluated the cytotoxic and molecular effects of andrographolide on two human prostate cancer cell lines, PC3 and LNCaP, along with HEK-293 cells as a noncancerous model. Results: Cell viability assessment using the MTT assay revealed dose-dependent cytotoxicity, with 24 h IC₅₀ values of 82.31 µM for PC3, 68.79 µM for LNCaP, and 133.9 µM for HEK-293 cells. Subsequent expression analysis of key oncogenic and tumor suppressor miRNAs demonstrated that andrographolide induced the upregulation of miR-16-5p, miR-34a-5p, and miR-200a-5p miRNAs implicated in apoptosis, proliferation control, and androgen receptor signaling. In contrast, the expression of oncomiRs miR-21-5p and miR-221-5p showed minimal or nonsignificant changes, reflecting the complex and context-specific roles of miRNAs in prostate cancer. Gene expression profiling further indicated differential transcriptional responses between the two prostate cancer cell lines, consistent with their distinct molecular backgrounds. Conclusions: Although HEK-293 cytotoxicity and previously reported nephrotoxic effects warrant caution, these results support the potential of andrographolide as an adjuvant phytochemical capable of modulating clinically relevant miRNAs in prostate cancer. Future studies investigating optimized delivery systems and validating direct miRNA targets may help advance andrographolide toward safer and more targeted therapeutic applications. Full article

A high-performance liquid chromatography method coupled with diode array detection (HPLC-DAD) was developed for simultaneous quantification of andrographolide (AG) and 14-deoxy-11,12-didehydroandrographolide (DDAG) in rat plasma. A salt-assisted liquid–liquid extraction (SALLE) procedure was optimized, with MgSO₄ yielding the highest extraction efficiency (>90% for both AG and DDAG), outperforming conventional solvent extraction, and being comparable to solid-phase extraction. The method exhibited acceptable linearity (125–2000 ng/mL, R² > 0.99), with low limits of detection and quantification of 60 and 70 ng/mL for AG and 201 and 234 ng/mL for DDAG, respectively, while adhering to the ICH M10 criteria for accuracy, precision, and stability under various storage conditions. Stability testing of the prepared samples demonstrated that >99% AG and 95% DDAG were retained when stored at low temperatures, specifically below 4 °C. The developed method was successfully applied in a pharmacokinetic study following oral administration of Andrographis paniculata extract (containing AG 7.5 mg/kg) to healthy Wistar rats. The SALLE-HPLC-DAD method developed herein enables selective AG quantification without significant matrix interference. In conclusion, this study introduces an alternative sample preparation and analytical method that is fast, cost-effective, and reliable, making it suitable for pharmacokinetic studies of the principal biomarker of Andrographis paniculata. Full article

Dehydroandrographolide (DA), a bioactive diterpenoid from Andrographis paniculata with diverse biological activity, was investigated for its antioxidant and anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and dextran sulfate sodium (DSS)-induced murine colitis. In vitro, DA inhibited the inflammatory response by modulating extracellular Signal-Regulated Kinase (Erk), c-Jun N-terminal Kinase (Jnk), p38 Mitogen-Activated Protein Kinase (P38), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 activation, and downregulated interleukin-6 (il-6) and interleukin-1β (il-1β) mRNA. It also had antioxidant effects by upregulating Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2), NAD(P)H quinone dehydrogenase 1 (Nqo-1) and heme oxygenase-1 (Ho-1), promoting protein kinase B (Akt) and 5′-adenosine monophosphate-activated protein kinase-α1 (Ampk-α1) phosphorylation. DA decreased cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNos) levels and alleviated intracellular reactive oxygen species (ROS) accumulation. In vivo, DA alleviated DSS-induced colitis in wild type (WT) mice by improving weight loss, disease activity index, colonic inflammation, and oxidative stress. The beneficial effects were linked to inhibiting Erk, Jnk, and P38 activation and enhancing Nrf2 signaling pathway. DA inhibited NOD-like receptor family pyrin domain-containing 3 (Nlrp3) inflammasome-mediated pryoptosis. However, DA’s protective effects were abolished in DSS-induced nrf2^−/− mice, suggesting its efficacy depends on Nrf2 signaling. Overall, DA alleviates oxidative stress, inflammatory responses, and pyroptosis in experimental colitis mice mainly by activating Nrf2 signaling pathway, highlighting its potential as a promising therapeutic option for inflammatory bowel disease. Full article

Andrographis paniculata, a medicinal plant widely found in Asia, contains andrographolide as its main active compound, known for its wide-ranging pharmacological effects, including anti-inflammatory, anti-cancer, anti-obesity, and anti-diabetic properties. Recent investigations have highlighted the anti-infective potential of andrographolide and its derivatives, with demonstrated antiviral, antibacterial, and antimalarial activities. This review summarizes progress in andrographolide’s anti-infective applications, focusing on its structure–activity relationship (SAR) and mechanisms of action. Researchers have used semi-synthetic methods, such as esterification, oxidation, Michael addition, salification, and hybrid design, to enhance andrographolide’s physicochemical properties and biological activity. These derivatives show potent antiviral activity against RNA and DNA viruses, antibacterial activity against Gram-positive and Gram-negative bacteria, antifungal effects, and antiparasitic activity against Plasmodium spp. and Leishmania spp. Nevertheless, poor solubility and limited bioavailability still hinder their clinical translation. Strategies such as nano delivery systems and β-cyclodextrin complexes are discussed to improve bioavailability. Although andrographolide itself has not received regulatory approval as a stand-alone drug, several andrographolide-containing preparations have been clinically used in certain countries. Overall, this review brings together evidence on antiviral, antibacterial, antifungal, and antiparasitic activities, linking them with structure–activity trends and pharmacokinetic insights, thereby providing a consolidated foundation for future development and clinical translation. Full article

Obesity is closely associated with the development of insulin resistance (IR) and type 2 diabetes mellitus (T2DM), primarily due to dysfunctional adipose tissue expansion and the secretion of pro-inflammatory cytokines such as interleukin-1β (IL-1β). 14-Deoxy-11,12-didehydroandrographolide (deAND), a major diterpenoid component of Andrographis paniculata, has demonstrated notable antioxidant and anti-inflammatory activities. This study aimed to investigate the protective effects and mechanisms of deAND against IL-1β-induced IR in 3T3-L1 adipocytes. Network pharmacology analysis indicated that deAND targets several IR-related signaling pathways, particularly the MAPK and IRS-1/AKT pathways. The experimental results show that IL-1β stimulated p67phox membrane translocation and reactive oxygen species (ROS) production, contributing to impaired insulin signaling by activating ERK and JNK and reducing IRS-1/AKT phosphorylation, which ultimately decreased insulin-stimulated glucose uptake. Pretreatment with deAND effectively inhibited NOX2-derived ROS generation, suppressed ERK/JNK activation, restored IRS-1/AKT phosphorylation, and reversed the reduction in glucose uptake caused by IL-1β. These findings suggest that deAND can alleviate IR by inhibiting NOX2-mediated oxidative stress, restoring insulin signaling and improving glucose uptake, highlighting its potential as a therapeutic agent for obesity-related IR. Full article

Skin aging is characterized by compromised epidermal homeostasis and dermo-epidermal junction (DEJ) integrity, resulting in reduced stem cell potential and impaired tissue regeneration. This study investigated the effects of Andrographis paniculata extract (APE) on keratinocyte stem cells (KSCs) and DEJ composition in human skin. Using human skin explants and cell culture models, we demonstrated that APE treatment enhances DEJ composition by increasing Collagen IV and Laminin production while decreasing MMP-9 expression, without altering epidermal structure or differentiation. In the same model, APE preserved stemness potential by upregulating markers related to niche components (collagen XVII and β1-integrin), proliferation (Ki-67 and KRT15), and stem cell capacity (Survivin and LRIG1). In vitro studies revealed that APE selectively stimulated KSC proliferation without affecting transit amplifying cells and promoted Collagen IV and Laminin secretion, particularly in KSCs. Furthermore, in a co-culture model simulating a compromised DEJ (UVB-induced), APE increased Laminin production in KSCs, suggesting a protective effect against photo-damage. These findings indicate that APE enhances DEJ composition and preserves stem cell potential, highlighting its promise as a candidate for skin anti-aging strategies targeting stem cell maintenance and extracellular matrix stability to promote skin regeneration and repair. 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

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

A characteristic of Chronic Obstructive Pulmonary Disease (COPD) is the inflammation of the respiratory pathway. Inflammatory regulators affected in COPD include cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), interleukin (IL-1β), and interleukin-6 (IL-6). Therefore, this systematic review aimed to investigate the biological activity of Indonesian medicinal plants as anti-inflammation through in vitro, in silico, and in vivo studies. A digital search was conducted using Scopus, Google Scholar, and PubMed online databases to find relevant articles by applying specific keywords related to the subject of interest. The results showed 18 studies that reported five Indonesian medicinal plants proven to inhibit inflammation regulation. The five plants were sambiloto (Andrographis paniculata), legetan warak (Adenostemma lavenia), kersen (Muntingia calabura), babadotan (Ageratum conyzoides), and sembung rambat (Mikania micrantha Kunth). In vitro studies, A. paniculata, A. lavenia, and M. calabura can suppress the levels of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, in LPS-stimulated RAW 264.7 cells. In silico studies, compounds that have strong binding to bind inflammatory receptors are andrographiside contained in A. paniculata; ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid contained in A. lavenia; 7-Hydroxyflavone contained in M. calabura; and 22,23-Dihydrospinasterol contained in A. conyzoides. In vivo studies, extracts of A. paniculata, M. calabura, A. conyzoides, and M. calabura can reduce inflammation in lung tissue in animal models (hamsters, mice, and rats). This systematic review might help to develop COPD treatment and build scientifically natural products from Indonesian medicinal plants for future investigations. Full article