indirubin

Natural products provide a new opportunity for the discovery of neuraminidase (NA)inhibitors. In this study, an affinity ultrafiltration (AUF) coupled with HPLC-MS/MS method was firstly developed and optimized for screening of NA inhibitors from natural products. The critical factors influencing the interaction of enzyme-ligand (including sample concentration, enzyme concentration, incubation time and temperature, pH of the buffer, and dissociation solvents and time) were investigated and optimized by a one-factor-at-a-time design...

BACKGROUND: Strobilanthes cusia (Nees) Kuntze is a traditional medical plant distributed widely in south China. The indole compounds that originated from the plant are responsible for its pharmacological activities. However, the reason why indole ingredients are accumulated in this herb and how it is biosynthesized has remained largely unknown. RESULTS: In this study, metabolic and transcriptional profiling measurement experiments of different S. cusia organs were carried out to understand the underlying molecular basis of indoles' biosynthetic logic...

Based on the facts that significant synergistic effect existed between PARP inhibitors and DNA damage agents and the DNA damage caused by indirubin's derivatives, we herein adopted the strategy to combine the pharmacophores of PARP inhibitors and the unique scaffold of indirubin to design a series of bifunctional molecules inducing DNA damage and targeting PARP. After SAR studies, the most potent compound 12a, encoded as KWWS-12a, exhibited improved inhibitory effect against PARP1 compared with PARP1 inhibitor Olaparib (IC50  = 1...

Skin cancer is the most common malignant disease worldwide and, therefore, also poses a challenge from a pharmacotherapeutic perspective. Derivatives of indirubin are an interesting option in this context. In the present study, the effects of 3-[3'-oxo-benzo[ b ]thiophen-2'-( Z )-ylidene]-1-(β-d-glucopyranosyl)-oxindole (KD87), a thia-analogous indirubin N -glycoside, on the viability and mitochondrial properties of melanoma (A375) and squamous cell carcinoma cells (A431) of the skin were investigated...

Glutathione peroxidase 4 (GPX4) is an essential antioxidant enzyme that negatively regulates ferroptosis. To exploit novel GPX4 inhibitors, we designed and synthesized 32 indirubin derivatives. Compound 31 exhibited the strongest antitumor activity against HCT-116 cells (IC50  = 0.49 ± 0.02 μM). Further studies suggested that 31 could induce ferroptosis in colon cancer cells and its cytotoxic activity could be reversed by ferroptosis inhibitors. Mechanism research showed that 31 promoted the degradation of GPX4, causing the accumulation of lipid ROS to induce ferroptosis...

The present investigation aimed to determine the effectiveness of bioactive components extracted from Hom herbs (Strobilanthes cusia (Nees) Kuntze) using the solvent-free microwave-assisted extraction (MAE) method. The obtained bioactive components were analyzed for total phenolic content (TPC) and active ingredient content. The Hom extracts were examined for antioxidant, antibacterial, anti-inflammatory, cytotoxic, and anticancer activities. The comparative analysis of extraction methods MAE was studied by using different solvents such as ethanol (EtOH), 50% ethanol (50EtOH) and distilled water (DW)...

Indigo Naturalis is not only an ancient plant dye but also a famous herbal medicine with antibacterial, anti-inflammatory, and anticancer properties. In traditional processes, thousands of manual stirring separate the high-quality Indigo Naturalis from the crude pulp system. However, this method is time-consuming and labor-intensive, resulting in an unstable quality and low yield, which cannot meet the requirements of modern industrial production. In this study, foam-separation technology was used to increase the industrial applicability of high-quality Indigo Naturalis...

Isatis spp. are well-known for their industrial significance due to natural sources of indigotin and indirubin, important indole alkaloids, used in the dye and pharmaceutical industries. In this study, silver nanoparticles (AgNP) and salicylic acid-chitosan nanoparticles (SA-CNP) were synthesized and applied to enhance the production of indigotin and indirubin in shoot and root cultures of Isatis tinctoria and Isatis ermenekensis. Different doses of AgNP and SA-CNP were administered to three-week-old shoot and root cultures, and the effects were assessed at 12, 24, and 48 h...

PURPOSE: To unravel the mechanism regulating the phosphorylation of glycogen synthase kinase 3 (GSK3) and the correlation between the inhibitory phosphorylation of GSK3α and sperm motility in human. MATERIALS AND METHODS: The phosphorylation and priming phosphorylated substrate-specific kinase activity of GSK3 were examined in human spermatozoa with various motility conditions. RESULTS: In human spermatozoa, GSK3α/β was localized in the head, midpiece, and principal piece of tail and p-GSK3α(Ser21) was enriched in the midpiece...

Purple urine bag syndrome (PUBS) is an uncommon, but usually benign, underrecognized clinical condition with the distressing presentation of purple, blue or reddish discoloration of a patient's catheter bag and tubing in the setting of catheter-associated urinary tract infections (UTIs). PUBS is the result of the complex metabolic pathway of the dietary essential amino acid tryptophan. Its urinary metabolite, indoxyl sulfate, is converted into red and blue byproducts (indirubin and indigo) in the presence of the bacterial enzymes indoxyl sulfatase and phosphatase...

Indigo (IND) and indirubin (INB) have demonstrated a synergistic effect in treating ulcerative colitis at a ratio of 7.5:1. However, the colon mucus layer, a critical physiological barrier against external threats, is also a biological barrier, limiting the potential for effective drug delivery to the lamina propria for regulating inflammatory cells. Inspired by the potential of Hyaluronic acid (HA), to enhance cellular uptake by inflammatory cells, and Pluronic® F127 (F127), known for overcoming the mucus barrier, this study innovatively developed INB/IND nanosuspensions by co-modifying with F127 and HA...

OBJECTIVES: Liver fibrosis is a common liver disease caused by chronic liver damage. However, there are currently no approved drugs available to treat it. Therefore, the therapeutic effect of indirubin on liver fibrosis was evaluated. This study investigated the protective effect and related molecular mechanism of indirubin against CCl4 -induced liver fibrosis in mice. MATERIALS AND METHODS: We first detected the effect of indirubin on liver fibrosis in mice (n=8 per group, 32 mice total) by ELISA, HE, and Masson staining...

ETHNOPHARMACOLOGICAL RELEVANCE: Asthma is a chronic airway inflammatory disease that can lead to several complications caused by bacterial infections. However, recurrent attacks of the disease require long-term use of antibiotics, resulting in lung dysbiosis and poor outcomes. Daqing Formula (DQF) is a well-known herbal medicine in Pharmacopoeia of China, which is widely used for various stimuli-induced lower respiratory diseases, including asthma, bronchitis, and pneumonia. Thus, it has been demonstrated to be a plant-derived broad-spectrum antibiotic for treating and preventing various acute and chronic respiratory diseases...

Indigo naturalis (IN) has been extensively used as a topical treatment for psoriasis. However, clinical applications of IN in ointment were hampered by its limited transdermal efficiency and dark stains. To address the aforementioned issues, nanopatches carrying IN were fabricated using poly(ε-caprolactone, PCL)/poly(ethylene oxide, PEO) and topically applied to psoriasiform skin. The ideal ratio of 5% PCL/PEO was established to be 80:20 (w/w), and 15% IN as payload was confirmed. Investigations on the three principal active components of IN release indicated that indirubin and tryptanthrin were released in bursts, while indigo was released in a limited and controlled manner...

BACKGROUND: Psoriasis is a chronic and incurable skin disorder that causes inflammation. There is an urgent clinical need for new treatments. We identified the natural compound indirubin as a potential potent agent for the treatment of psoriasis, but it's therapeutic effect and underlying mechanisms were not well understood. METHODS: Peripheral blood and skin tissues from psoriasis patients and healthy individuals were collected. Bioinformatics analysis was performed to investigate LAT1 expression and associated signal pathways in psoriasis skin lesions...

CONTEXT: Aryl hydrocarbon receptor (AhR) agonists are potential therapeutic agents for ulcerative colitis (UC). Indirubin (IDR), which is a natural AhR ligand approved for leukemia treatment, ameliorates dextran sulfate sodium (DSS)-induced colitis in mice. However, the therapeutic mechanisms of IDR are unknown, limiting its application. OBJECTIVE: This study explores the therapeutic mechanisms of IDR in DSS-induced colitis using transcriptomic analysis. MATERIALS AND METHODS: Male BALB/c mice were categorized to six groups: normal, DSS model (2% DSS), IDR treatment (10, 20 and 40 mg/kg), and sulfasalazine (520 mg/kg) groups...

BACKGROUND: Ferroptosis, a type of programmed cell death triggered by oxidative stress, was suspected to play a role in ulcerative colitis. Indigo naturalis is highly effective against ulcerative colitis, but its mechanism is unclear. This study found that indigo naturalis treatment suppressed ferroptosis. METHODS: We analyzed 770 mRNA expressions of patients with ulcerative colitis. Suppression of ferroptosis by indigo naturalis treatment was shown using a cell death assay...

Acute myeloid leukemia (AML) is a prevalent form of leukemia in adults. As its survival rate is low, there is an urgent need for new therapeutic options. In AML, FMS-like tyrosine kinase 3 (FLT3) mutations are common and have negative outcomes. However, current FLT3-targeting agents, Midostaurin and Gilteritinib, face two significant issues, specifically the emergence of acquired resistance and drug-related adverse events leading to treatment failure. Rearranged during transfection (RET), meanwhile, is a proto-oncogene linked to various types of cancer, but its role in AML has been limited...

Central precocious puberty (CPP) is a widespread developmental abnormality. The application of gonadotrophin-releasing hormone agonist (GnRHa) is widely useful for the medical therapy of CPP. This study aimed to investigate the combination effect and mechanism of indirubin-3'-oxime (I3O), an active ingredient analogue of traditional Chinese medicine, and GnRHa treatment on the progression of CPP. First, female C57BL/6 mice were fed with a high-fat diet (HFD) for the induction of precocious puberty and treated with GnRHa and I3O alone or in combination...

Despite advances in transdermal drug delivery for treating psoriasis, there are still unmet medical needs, hyaluronic acid (HA)-based topical formulations as nanocarriers, which can increase drug concentration in psoriatic skin through CD44-assisted targeting. Here, HA was utilized as a matrix for nanocrystal-based hydrogel (NC-gel) to deliver indirubin topically for psoriasis treatments. Indirubin nanocrystals (NCs) were prepared through wet media milling and were then mixed with HA to create indirubin NC/HA gels...