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Synonym name: Tinosporin
Catalogue No.: BP0383
Cas No.: 546-97-4
Formula: C20H22O6
Mol Weight: 358.39
Botanical Source: Columbo root, Jateorhiza palmata and from Tinospora cordifolia
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.
For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.
HPLC of Columbin
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
92.8300
1.8500
1.7900
Low
No
No
No
Unknown
No
Unknown
Columbin is a naturally occurring diterpene furan lactone compound, first isolated from plants in the Rutaceae family. As a class of natural products with significant biological activity, glucumbine has attracted widespread attention due to its oral activity and diverse pharmacological effects. In recent years, with the deepening of pharmacological research on natural products, glulambene has demonstrated unique potential in anti-inflammatory, antiparasitic, and antimalarial fields. Its ability to selectively inhibit cyclooxygenase-2 (COX-2) enzyme provides the molecular basis for its anti-inflammatory effects; At the same time, the effects of glumbine on various malaria parasite-related targets suggest its value in the development of antimalarial drugs. This paper will systematically review the chemical structure and physicochemical properties of gullambine, plant origins and extraction methods, pharmacological activity, and mechanism of action, combined with druggability evaluation and pharmacokinetic data, to explore its clinical application prospects and future research directions.
Glumbin (CAS No.: 546-97-4) belongs to the diterpene furan lactone class, with a molecular formula of C20H22O6 and a molecular weight of 358.38. Its structural features include a typical furanolide ring system and polycyclic diterpene backbone, which have multiple hydroxyl and carbonyl functional groups, giving it high polarity and biological activity. In terms of physicochemical properties, the LogP value of gluembine is 1.85, indicating moderate hydrophobicity and facilitating oral absorption; the topological polar surface area (TPSA) is 92.83 Ų, indicating certain polarity that facilitates binding with biological macromolecules. Glumbine contains six hydrogen bond receptors and may be involved in the binding of various enzymes and receptors. Additionally, Glumbin's blood-brain barrier penetration ability is relatively low, suggesting its limited distribution in the central nervous system, which to some extent reduces the risk of CN toxicity. Toxicological evaluation showed that glucumbine showed no significant hepatotoxicity, cardiotoxicity, or hERG channel inhibition, and its safety was relatively high.
Gullambine is mainly found in Rutaceae plants, such as Calumbae radix and its related species. In traditional Chinese medicine, these plants are often used to treat inflammation, parasitic infections, and other diseases. The extraction of glumbine is usually done using organic solvent extraction combined with multi-stage column chromatography purification technology to obtain high-purity compounds. Specific methods include:
In recent years, supercritical fluid extraction and microwave-assisted extraction technologies have also been applied to the extraction of columbine, improving extraction efficiency and purity.
As a selective COX-2 inhibitor, columbine exhibits significant anti-inflammatory activity. In vitro experiments showed that the half-effective concentration (EC50) of gullambine for COX-2 was 53.1 μM, much lower than its inhibitory concentration for COX-1 (EC50=327 μM), indicating high selectivity for COX-2. COX-2 is an induced cyclooxygenase in inflammatory responses, catalyzing the production of prostaglandins and participating in the production of inflammatory mediators. Glumbin exerts anti-inflammatory effects by inhibiting COX-2 activity and reducing the synthesis of inflammatory mediators. In animal models, glumbine significantly inhibited the expression of inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), reducing pathological damage to inflammatory tissues.
Trypanosoma infection is the pathogen of various tropical diseases, and Glumbin shows good inhibitory effects against trypanonomyceros. In vitro studies have shown that glucumbine can inhibit the growth and reproduction of trypanosomes, possibly by interfering with parasite energy metabolism and cell membrane function. This action provides a theoretical basis for gullumbine in the development of antiparasitic drugs.
Columbine has shown multi-target action in antimalarial research. Malaria is caused by the parasite Plasmodium spp., which involves multiple key protein targets throughout its life cycle. Glumbine has been found to act on malaria parasite-related targets such as PFCRT, PFMDR1, PFDHFR, PFK13, PFATP6, PFCYTBC, PFPK, PFCYT, PFCYTb, and PfATG8. These targets cover drug transport, metabolic enzymes, protein kinases, and autophagy-related proteins, suggesting that glumbin may inhibit the growth and survival of malaria parasites through multiple mechanisms. Although direct in vivo evidence for malaria is still insufficient, its multi-target nature offers new ideas for antimalarial drug design.
By specifically binding to the active site of COX-2, glimpsine blocks a key step in prostaglandin synthesis. Molecular docking and kinetic simulations showed that the furanolactone ring of glumbin forms a stable bond with the hydrophobic pocket of COX-2, while its hydroxyl groups enhance affinity with enzyme active centers through hydrogen bonding. Compared to COX-1, the structural differences of COX-2 make it easier for Glumbine to enter its active pocket, explaining its higher selectivity.
The mechanism by which gullambine acts on several key proteins of the malaria parasite is still under investigation. PFCRT and PFMDR1 are membrane transporters involved in drug uptake and excretion. Glumbine may reverse drug tolerance by regulating the function of these proteins. PFDHFR is a key enzyme in folate metabolism; inhibiting its activity can block nucleic acid synthesis in Plasmodium. PFK13 and PFATP6 act as protein kinases and calcium pumps, respectively, affecting signal transduction and ion homeostasis in Plasmodium. PFCYTBC, PFPK, PFCYT, and PFCYTb involve the mitochondrial electron transport chain, and glombine may cause malaria parasite death by interfering with energy metabolism. PfATG8 participates in autophagy and regulates intracellular homeostasis; its effect on glombine may affect the survival mechanisms of malaria parasites.
Glumbin's inhibition of trypanozoa may be related to interference with the integrity of the parasitic cell membrane and energy metabolism. Studies have shown that glumbin can induce increased permeability of parasite cell membranes, leading to leakage of cellular contents and death. Additionally, glumbin may inhibit mitochondrial function of parasites, reduce ATP production, and suppress their growth.
Glumbine exhibits relatively ideal characteristics in terms of druggability. Its molecular weight is 358.38, which fits the ideal range of Lipinski's rules. A LogP value of 1.85 indicates moderate lipid solubility, which is beneficial for oral absorption. TPSA was 92.83 Ų, indicating good cell membrane permeability. The number of hydrogen bond receptors is 6, which is moderate and facilitates stable binding to target proteins.
Toxicological evaluations showed that glucumbine had no significant hepatotoxicity or cardiotoxicity, and did not inhibit hERG channels, reducing the risk of cardiac safety of the drug. Its lower blood-brain barrier penetration capacity reduces the likelihood of central nervous system side effects. Ames-induced mutagenic data are still lacking, but existing safety data support its potential as a candidate drug.
Pharmacokinetics, oral glulambine has good bioavailability, with its distribution mainly limited to peripheral tissues. Its metabolic pathways may involve hydroxylation of hepatic enzymes and glucuronic acid binding. Excretion mainly occurs through the kidneys and bile. In the future, further systematic assessment of its in vivo metabolic kinetics parameters and drug interaction risks is needed.
As a natural diterpene furanolide, glumbine, with its multiple pharmacological activities including anti-inflammatory, antiparasitic, and antimalarial effects, shows broad clinical application prospects. In the field of anti-inflammatory treatment, the selective COX-2 inhibitory effect of glumbine makes it a promising candidate for nonsteroidal anti-inflammatory drugs (NSAIDs), especially suitable for patients who need to reduce gastrointestinal side effects. Its antitrypanosoma activity offers a new drug option for treating tropical parasitic diseases. In terms of antimalarial treatment, the multi-target mechanism of gullambin offers potential strategies to address drug resistance in malaria.
Future research should focus on in vivo pharmacodynamic validation, toxicological system evaluation, and preclinical safety studies of glumbine. At the same time, designing and synthesizing columbine derivatives based on their structural characteristics to optimize pharmacodynamics and pharmacokinetic performance will help promote their clinical translation. Combining modern drug delivery systems, such as nanocarriers or targeted drug delivery technologies, can also enhance the bioavailability and tissue selectivity of glumbine.
As a natural product with significant biological activity, gullambine, with its unique chemical structure and diverse pharmacological effects, has demonstrated significant research value and application potential in anti-inflammatory, antiparasitic, and antimalarial fields. Its excellent druggability parameters and safety evaluation lay the foundation for subsequent drug development. In the future, through in-depth mechanistic research, structural optimization, and preclinical studies, Glumbin is expected to become an important representative of new natural medicines, providing new solutions for the treatment of related diseases.
Shenshuai
Wenjing
Hedandan
