Higenamine

ETHNOPHARMACOLOGICAL RELEVANCE: Allergic rhinitis (AR) is a prevalent nasal inflammatory disorder, and pyroptosis plays a crucial role in aggravating AR. Current medications for AR treatment still have deficiencies, and finding new agents is of great interest. Mahuang Fuzi Xixin decoction (MFXD), an ancient Chinese medicine, is now commonly used to treat AR, which has anti-inflammatory and immunomodulatory effects, but its underlying mechanism is unknown. AIM OF THIS STUDY: This study aims to evaluate the effects of MFXD on AR and explore its potential mechanisms in view of the regulatory effect on pyroptosis...

Higenamine (HG) is a β2 receptor agonist and was explicitly added to the Prohibited List of the World Anti-Doping Agency in 2017. This compound is prohibited in both in- and out-of-competition athletes and falls under the category of nonthreshold substances. Because of HG presence in numerous plants, as evidenced by a growing body of research data, an exception was made for HG in the TD2017MRPL document, in which adverse analytical findings (AAFs) were not reported if the urinary HG concentration was less than 10 ng/mL...

In 2017, higenamine was added to the World Antidoping Agency's (WADA) Prohibited list under group S3: beta-2 agonists and it is banned for athletes both in - and out of competition. Aim of this study was to characterize the urinary excretion profile of higenamine and its metabolite coclaurine after oral administration of multiple doses of higenamine capsules. For this purpose, an administration study including female basketball players was performed. For the detection of higenamine and cocalurine in the collected urine samples, a new, fast, and highly sensitive quantitative on-line SPE LC HRMS method was developed and validated...

This study compared the changes in chemical components during the processing of different types of Aconiti Lateralis Radix Praeparata(ALRP) in "Jianchang" faction, i.e., dried ginger-steamed ALRP pieces(Yin-FP), sand-fried ALRP pieces(Yang-FP), and rice swill water-bleached ALRP pieces(DFP), and provided a scientific basis for the mechanism in toxicity reduction and efficacy enhancement from a compositional perspective. Samples were collected during the processing of the three types of ALRP pieces, yielding raw ALRP pieces, water-bleached Yin-FP, ginger juice-moistened Yin-FP, steamed Yin-FP, water-bleached Yang-FP, sand-fried Yang-FP, water-bleached DFP, rice swill water-bleached DFP, and roasted DFP...

Pain is the cardinal symptom of many debilitating diseases and results in heavy health and economic burdens worldwide. Asarum (Asarum sieboldii Miq.) is a commonly used analgesic in traditional Chinese medicine. However, the analgesic components and mechanisms of asarum in acute and chronic pain mice model remain unknown. In this study, we first generated asarum water extract and confirmed strong analgesic properties in mice in both the acute thermal and acute pain models, as well as in the complete Freund's adjuvant (CFA) induced chronic inflammatory pain model...

BACKGROUND: Depression is a refractory psychiatric disorder closely associated with dysfunction of the gap junctions (GJs) between astrocytes as well as neuroinflammation. Higenamine (Hig) is a potent cardiotonic ingredient in Fuzi (i.e., Aconitum carmichaeli Debx.) with anti-inflammatory and antioxidant effects, which has a significant protective effect on damaged nerve cells and has great potential for the treatment of neuropsychiatric diseases. METHODS: Rats were stimulated by chronic unpredictable stress (CUS) for 28 days while given Hig (5, 10, 20 mg/kg) and then analyzed behaviorally by the open field test, sucrose preference test, and forced swimming test...

Athletes need to consume a significant amount of energy during prolonged training and in high-intensity competition. It is necessary for them to take nutritional foods that recharge their bodies. However, in sporting events of recent years, both domestic and international, many positive drug tests are found to be caused by the ingestion of foods that contain performance-enhancing drugs (PEDs). As a result, the prevention and control of PEDs in food supply have drawn increasing attention. For better prevention and control, the first step is to understand the food contaminants -- PEDs...

BACKGROUND: Taiwan's unique health behaviour, such as extensive exposure to Chinese Herbal Medicine (CHM), has introduced a risk of inadvertent doping among competing athletes. Pharmacy professionals have an imperative role in advising athletes on the safe use of medicines. This study provides an overview of anti-doping knowledge and educational needs among pharmacists in Taiwan and examines influencing factors. METHODS: A cross-sectional online questionnaire survey consisting of five domains, namely demographic characteristics, source of prohibited substances, identification of prohibited substances, understanding of doping control, and education needs on anti-doping, was distributed to the registered pharmacists in Taiwan...

ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora crispa (L.) Hook. f. & Thomson stem (TCS) has long been used as folk medicine for the treatment of diabetes mellitus. Previous study revealed that TCS possesses multi-ingredients and multi-targets characteristic potential as insulin sensitizer activity. However, its mechanisms of action and molecular targets are still obscure. AIM OF THE STUDY: In the present study, we investigated the effects of TCS against insulin resistance in muscle cells through integrating in vitro experiment and identifying its active biomarker using metabolomics and in molecular docking validation...

Higenamine (Hige), a plant derived alkaloid is classified as β2 agonist by the World Anti-Doping Agency (WADA). However, pharmacologic mechanisms of its performance-enhancing activity have not been investigated so far. Therefore, we investigate the anabolic activity and associated molecular mechanisms of Hige in C2C12 myotubes. In differentiated C2C12 cells dose-dependent effects of Hige on myotube size were analyzed. The mRNA expression of genes involved in hypertrophy was measured. For mechanistic studies, β2-adrenoceptor (ADRB2), androgen receptor (AR), and estrogen receptor (ER) inhibitors and dexamethasone (Dexa) were co-incubated and myotube diameter was evaluated...

Higenamine is prohibited in sports as a β2 -agonist by the World Anti-Doping Agency. As a key component of a great variety of plants, including the Annonaceae family, one aim of this research project was to evaluate whether the ingestion of Annona fruit could lead to higenamine adverse analytical findings. Single-dose administration studies including three Annona species (i.e., Annona muricata, Annona cherimola, and Annona squamosa) were conducted, leading to higenamine findings below the established minimum reporting level (MRL) of 10 ng/mL in urine...

Environmental pollutants such as fine dust are increasingly linked to premature skin aging. In this study, we investigated the protective effects of higenamine, a natural plant alkaloid, against fine-dust-induced skin aging in human keratinocytes (HaCaT cells). We found that higenamine significantly attenuated fine-dust-induced expression of matrix metalloproteinase-1 (MMP-1), a key enzyme involved in collagen degradation. Furthermore, higenamine was found to modulate fine-dust-induced AP-1 and NF-κB transactivation, which are crucial factors for MMP-1 transcription...

The first nootropic prohibited in sport was fonturacetam (4-phenylpiracetam, carphedon) in 1998. Presented here 25 years later is a broad-scale consideration of the history, pharmacology, prevalence, regulations, and doping potential of nootropics viewed through a lens of 50 selected dietary supplements (DS) marketed as "cognitive enhancement," "brain health," "brain boosters," or "nootropics," with a focus on unauthorized ingredients. Nootropic DS have risen to prominence over the last decade often as multicomponent formulations of bioactive ingredients presenting compelling pharmacological questions and potential public health concerns...

Histone lysine-specific demethylase 1 (LSD1) is a promising target for cancer therapy. Here, we performed the design, synthesis, and extensive structure-activity relationship (SAR) studies based on our previously discovered natural LSD1 inhibitor, higenamine. We found that the tetracyclic tetrahydroisoquinoline FY-21 is a potent and selective inhibitor of LSD1 (IC50  = 340 nM). FY-21 inhibited leukemia cell proliferation and colony formation and increased the level of p53 expression. Meanwhile, FY-21 reduced the mRNA levels of the transcription factors HOXA9 and MEIS1...

Ulcerative colitis (UC) is an inflammatory disease of the colon and tends to relapse. Higenamine (HG) has anti-inflammatory, antioxidant and anti-apoptotic activities. This study aimed to investigate the role of HG in the treatment of UC as well as the underlying mechanism. In vivo and in vitro models of UC were respectively established in dextran sodium sulfate (DSS)-induced mice and DSS-induced NCM460 cells. The weight and disease performance and disease activity index (DAI) of mice were recorded every day...

Fusobacterium nucleatum (F. nucleatum) is closely associated with the occurrence and development of colorectal cancer (CRC). Discovery of specific antibacterial agents against F. nucleatum was urgent for the prevention and treatment of CRC. We screened a natural product library and successfully identified higenamine as an antibacterial hit against F. nucleatum. Further hit optimizations led to the discovery of new higenamine derivatives with improved anti-F. nucleatum activity. Among them, compound 7c showed potent antibacterial activity against F...

Osteoporosis is a common bone disease caused by an imbalance of bone resorption and formation that results in a loss of total bone density. SMAD2/3 signal transduction is known to plays a crucial role in osteogenic differentiation through transforming growth factor-beta (TGF-β). By screening a library of small-molecule compounds, the current study identifies Higenamine (HG) as an active osteogenic agent that may be a potential therapeutic candidate for osteoporosis. In vitro data demonstrated that HG effectively induced expressions of osteogenic markers in mouse bone marrow stromal cell (BMSCs) and pre-osteoblastic cell cultures...

Members of the genus Aconitum have been used for millennia, both as poisons and medicines, in Eastern culture. Higenamine has non-selective beta-agonist effects, activating both β1 and β2 adrenoreceptors, and is present in a variety of plants. The World Anti-Doping Agency has banned Higenamine both in competition and out of competition. Due to the common uses of higenamine in Brazilian culture, both as medicine and food, we studied the urinary concentrations of higenamine after the consumption of fruits of the Annona genus...

Geo-authentic herbs refer to medicinal materials produced in a specific region with superior quality. Stephania tetrandra S. Moore ( S. tetrandra ) is cultivated in many provinces of China, including Anhui, Zhejiang, Fujian, Jiangxi, Hunan, Guangxi, Guangdong, Hainan, and Taiwan, among which Jiangxi is the geo-authentic origin. To explore habitat-related chemical markers of herbal medicine, an integrated chromatographic technique including gas chromatography-mass spectrometry (GC-MS), ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) combined with chemometric analysis was established...

Myocardial perfusion imaging (MPI) is valuable for the diagnosis, prognosis, and management of coronary artery disease (CAD). The most commonly used pharmacologic stress agents at present are vasodilators and adrenergic agents. However, these agents have contraindications and may cause adverse effects in some patients. Thus, other stress agents feasible for more patients are required. Higenamine (HG) is a β-adrenergic receptor agonist currently approved for clinical trials as a stress agent for myocardial infarction...