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Product name: Nomilin
Synonym name:
Catalogue No.: BP1003
Cas No.: 1063-77-0
Formula: C28H34O9
Mol Weight: 514.571
Botanical Source: Euodiae fructus
Physical Description:
Type of Compound: Triterpenoids
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.
The product could be supplied from milligrams to grams
Inquire for bulk scale.
Description:
Nomilin has immunomodulatory, antioxidant, anti-human immunodeficiency virus(HIV), cancer chemopreventive, antiangiogenic, anti-obesity and anti-hyperglycemic effects. Nomilin inhibits tumor-specific angiogenesis by downregulating VEGF, NO and proinflammatory cytokine profile and also by inhibiting the activation of MMP-2 and MMP-9. It inhibits osteoclastogenesis in vitro by suppression of NFATc1 and MAPK signaling pathways, indicates that nomilin-containing herbal preparations have potential utility for the prevention of bone metabolic diseases.
References:
Food Chemistry, 2005, 93(4):599-605.
Contents and antioxidant capacity of limonin and nomilin in different tissues of citrus fruit of four cultivars during fruit growth and maturation.
METHODS AND RESULTS:
The contents of limonin and Nomilin in different fruit tissues of Foxiangyou (Citrus grandis), Citrus unshiu, Penggan (Citrus reticulata) and Huyou (Citrus changshanensis KS Chen et CX Fu) were measured during fruit growth and maturation by HPLC (high performance liquid chromatography). Results showed that limonin and Nomilin were the predominant limonoids in the extracted samples. During fruit growth and maturation, the contents of limonin and Nomilin increased from April, peaked in early September and decreased afterwards until late October when they reached a steady low level. The antioxidant capacities of limonin and Nomilin in the four tissues of mature fruit were determined by beta-carotene bleaching assay.
CONCLUSIONS:
The results showed that the antioxidant capacities of limonin and Nomilin varied in different tissues and cultivars. In the three tissues other than albedo, the antioxidant capacities of limonin and Nomilin were high (2.9-8.3 times than that of vitamine C).
Planta Med. 2003 Oct;69(10):910-3.
Effect of limonin and nomilin on HIV-1 replication on infected human mononuclear cells.
In the last years several plant-derived natural compounds have been screened for their anti-HIV activity in order to find lead compounds with novel structures or mechanisms of action. Among these, several triterpenoids have been found to exhibit an antiretroviral activity with different mechanisms of action.
METHODS AND RESULTS:
In this study the effect of two limonoids, limonin and Nomilin, on the growth of human immunodeficiency virus-1 (HIV-1) in culture of human peripheral blood mononuclear cells (PBMC) and on monocytes/macrophages (M/M) is described. Limonin and Nomilin were found to inhibit the HIV-1 replication in all cellular systems used. A dose-dependent inhibition of viral replication was observed in PBMC isolated from healthy donors and infected with HIV-1 strain after incubation with limonin and Nomilin (EC (50) values: 60.0 microM and 52.2 microM, respectively). The two terpenoids inhibited at all concentrations studied the production of HIV-p24 antigen even when the PBMC employed were chronically infected (EC (50) values of 61.0 microM for limonin and 76.2 microM for Nomilin). Moreover, these compounds inhibited the HIV-1 replication even in infected M/M. In this cellular system the inhibitory effect was significant at the concentrations of 20 microM, 40 microM and 80 microM starting from day 14 and reached the maximum effect after 18 days of incubation. As regards the mechanism of action, limonin and Nomilin inhibit in vitro HIV-1 protease activity.
CONCLUSIONS:
In general, the results obtained point out a similar anti-HIV activity of limonin and Nomilin indicating that this activity is not drastically influenced by the structural difference between the two compounds.
Biochem Biophys Res Commun. 2011 Jul 8;410(3):677-81.
Anti-obesity and anti-hyperglycemic effects of the dietary citrus limonoid nomilin in mice fed a high-fat diet.
TGR5 is a member of the G protein-coupled receptor family and is activated by bile acids (BAs). TGR5 is thought to be a promising drug target for metabolic diseases because the activation of TGR5 prevents obesity and hyperglycemia in mice fed a high-fat diet (HFD).
METHODS AND RESULTS:
In the present study, we identified a naturally occurring limonoid, Nomilin, as an activator of TGR5. Unlike BAs, Nomilin did not exhibit the farnesoid X receptor ligand activity. Although the Nomilinderivative obacunone was capable of activating TGR5, limonin (the most abundant limonoid in citrus seeds) was not a TGR5 activator. When male C57BL/6J mice fed a HFD for 9 weeks were further fed a HFD either alone or supplemented with 0.2%w/w Nomilin for 77 days, Nomilin-treated mice had lower body weight, serum glucose, serum insulin, and enhanced glucose tolerance.
CONCLUSIONS:
Our results suggest a novel biological function of Nomilin as an agent having anti-obesity and anti-hyperglycemic effects that are likely to be mediated through the activation of TGR5.
Acs Symposium, 2000, 758:185-200.
Limonin and Nomilin Inhibitory Effects on Chemical-Induced Tumorigenesis.
The increased enzyme activity was correlated with the ability of these compounds to inhibit carcinogenesis.
METHODS AND RESULTS:
Nomilin was found to reduce the incidence and number of tumors per mouse of forestomach tumors induced by benzo[a]pyrene (BP). Topical application of the limonoids was found to inhibit both the initiation and the promotion phases of carcinogenesis in the skin of SENCAR mice. Nomilin appeared to be more effective at the initiation stage while limonin was more potent as an inhibitor at the promotion phase of carcinogenesis. Administration of Nomilin and limonin to the diet or by gavage inhibited BP-induced and 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone-induced lung tumor formations, respectively, in A/J mice.
CONCLUSIONS:
These findings suggest citrus limonoids are potential cancer chemopreventive agents.
HPLC of Nomilin
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
121.6400
2.5139
2.5139
.0053
2.5845
7.6217
High
79.1351
5.6420
No
No
No
No
Yes
No
0.0
Yes
No
No
Yes
Nomilin is a typical limonoid natural product, mainly found in citrus fruits such as lemons, limes, oranges, and grapefruits. As a secondary metabolite of citrus plants, nomirin has attracted widespread attention in recent years in pharmacology and natural product chemistry due to its unique chemical structure and diverse biological activities. Research shows that nomirin not only has significant anti-obesity and hypoglycemic effects, but also exhibits multiple pharmacological effects such as anti-tumor, anti-inflammatory, and antiviral properties, demonstrating high potential for clinical development.
With the continuous rise in the incidence of metabolic diseases and cancer, developing safe and effective natural medicines has become a current hotspot in pharmaceutical research. As a naturally occurring multifunctional compound, nomirin's regulatory role in multiple signaling pathways offers new approaches for the treatment of related diseases. This paper will systematically review the chemical structure and physicochemical properties of nomirin, its plant origins and extraction methods, delve into its pharmacological activity and mechanism of action, and, combined with druggability evaluation and pharmacokinetic data, look ahead to its clinical application prospects, aiming to provide theoretical basis and reference for further research and development of nomirin.
Nomirin has the molecular formula C28H34O9 and a molecular weight of 514.5710. Its structure belongs to the tetranortriterpenoid limonoid, characterized by a complex cyclic framework and multiple oxygen functional groups. Its core structure consists of four ring systems, with lactone rings and multiple hydroxyl and ether bonds, giving it strong polarity and diverse chemical reactivity. Nomirin has a LogP value of about 2.51, showing moderate lipid solubility and facilitating cell membrane penetration; its polar surface area (TPSA) is 121.64, indicating good hydrophilicity, which may affect its bioavailability.
In terms of physicochemical properties, nomirin has relatively low water solubility (about 0.0053 mg/mL), which to some extent limits its oral absorption and bioavailability. Its molecular structure is stable and does not exhibit hERG channel inhibitory activity, indicating a low risk of cardiotoxicity. Additionally, Ames-induced mutagenic test results were negative, suggesting that nomirin has good safety in terms of genotoxicity. Notably, nomirin has high blood-brain barrier permeability, which may give it potential application value in the treatment of central nervous system diseases.
Nomirin is mainly extracted from the fruits, peels, and seeds of citrus plants, with higher concentrations in grapefruit and lemons. Citrus plants, as widely cultivated economic crops worldwide, have by-products such as peels and pulp that are important sources of nomirin. Traditionally, the extraction of nomirin relies on organic solvent extraction, with commonly used solvents including methanol, ethanol, ethyl acetate, and chloroform.
The specific extraction process typically includes the following steps: first, the citrus peel or seeds are dried and crushed, followed by extraction by impregnation or reflux extraction to extract the crude extract. After concentration, the extract was separated and purified using silica gel column chromatography and reversed-phase high-performance liquid chromatography (RP-HPLC). In recent years, green and efficient technologies such as supercritical CO2 extraction and microwave-assisted extraction have gradually been applied to nomirin extraction, improving extraction efficiency and purity, reducing the use of organic solvents, and meeting the sustainable development requirements of modern natural product extraction.
Nomirin has shown significant effects in anti-obesity and diabetes prevention and treatment. In vitro and in vivo studies have shown that nomirin can inhibit adipocyte differentiation and lipid accumulation, regulate the expression of lipid metabolism-related genes such as PPARγ and C/EBPα, and reduce inflammatory responses in adipose tissue. Additionally, nomirin improves glucose metabolism disorders by enhancing insulin sensitivity and promoting glucose uptake, demonstrating potential hypoglycemic effects. In animal models, nomirin significantly reduced obesity and insulin resistance induced by high-fat diets, suggesting its value as an intervention agent for metabolic syndrome.
Nomirin exhibits the ability to inhibit proliferation, induce apoptosis, and inhibit migration across various tumor cell lines. Its antitumor mechanism involves multiple signaling pathways and molecular targets. The study found that nomirin can downregulate the expression of anti-apoptotic proteins MCL1 and BCL2, activating the cell apoptosis pathway; Inhibits the STAT3 signaling pathway, blocking tumor cell proliferation and survival; At the same time, by regulating matrix metalloproteinase MMP2, it inhibits tumor cell invasion and metastasis. In addition, nomirin also regulates key tumor-related proteins such as TOP1, TOP2A, HIF1A, and MAPK1, demonstrating multi-target synergistic anti-tumor effects.
Nomirin exhibits strong anti-inflammatory activity, inhibiting the production of inflammatory mediators such as TNF-α, IL-6, and NO, thereby reducing inflammatory responses. Its anti-inflammatory mechanism mainly works by inhibiting the NF-κB and MAPK signaling pathways. In terms of antiviral effects, nomirin has shown inhibitory effects against various viruses in vitro experiments, possibly by interfering with viral replication and regulating host immune responses, providing new directions for the development of natural antiviral drugs.
The multipharmacological activity of nomirin is attributed to its ability to regulate various molecular targets. In its antitumor effects, nomirin downregulates MCL1 and BCL2, disrupting the anti-apoptotic barrier of tumor cells and promoting programmed cell death. At the same time, inhibiting the STAT3 signaling pathway blocks tumor cell proliferation and immune escape. Inhibition of MMP2 reduces stromal degradation of tumor cells, limiting tumor invasion and metastasis.
Additionally, the regulation of NOMIRIN on TOP1 and TOP2A affects the activity of DNA topoisomerase, interfering with DNA replication and transcription in tumor cells. HIF1A inhibition blocks tumor cells' ability to adapt to hypoxic environments, suppressing tumor angiogenesis. Regulation of MAPK1 and ESR1 further affects cell signaling and the development of hormone-dependent tumors. Regulation of CYP19A1 (aromatase) may affect estrogen synthesis and has potential endocrine modulatory effects.
In terms of anti-obesity and blood sugar-lowering, nomirin improves metabolic homeostasis by regulating metabolic genes and inflammatory factors in adipose tissue. Its high blood-brain barrier permeability suggests it may regulate energy metabolism and appetite control through the central nervous system. Anti-inflammatory and antiviral mechanisms mainly rely on regulating immune signaling pathways, reducing inflammatory damage and inhibiting viral replication.
Druggability evaluation of nomirin indicates it has certain potential for drug development. Its molecular weight (514.57) is slightly above the recommended upper limit of the Lipinski rule (500), but its moderate LogP (2.51) and high polar surface area (121.64) help balance lipid and water solubility and promote distribution in vivo. Low water solubility is the main limiting factor for oral bioavailability, requiring pharmaceutical improvements such as nanocarriers, liposomes, or solid dispersions.
Pharmacokinetic studies have shown that nomirin has good blood-brain barrier penetration ability, suggesting its potential in treating central nervous system diseases. Metabolic pathways in the body mainly involve liver enzyme systems, and the activity and toxicity of these metabolites require further study. In terms of safety, nomirin does not inhibit the significant hERG channel, reducing the risk of cardiotoxicity; A negative Ames test indicates a low genotoxicity risk, supporting the safety of long-term medication.
Nomirin, with its multi-target and multifunctional pharmacological properties, shows broad clinical application prospects. Its potential in anti-obesity and hypoglycemic fields is particularly outstanding, and it may serve as an adjunct therapy for metabolic syndrome in the future. The multi-mechanism advantage of its antitumor action makes it an ideal candidate for multidrug resistance and combination therapy in tumors. Anti-inflammatory and antiviral activities provide new therapeutic approaches for chronic inflammatory diseases and viral infections.
However, the clinical translation of nomirin still faces many challenges, mainly including poor water solubility and low oral bioavailability. Future research should focus on drug formulation optimization, in-depth analysis of in vivo metabolic kinetics, and toxicological systematic evaluation. Additionally, the design and synthesis of derivatives based on the nomirin structure are expected to yield more efficient and safer drug candidates. Combining modern molecular biology and medicinal chemistry techniques, the clinical development prospects of nomirin and its analogs are promising.
Nomirin, as a natural limonoid product with abundant sources and diverse bioactivity, has become a hot topic in pharmacological research of natural products due to its significant anti-obesity, hypoglycemic, anti-tumor, anti-inflammatory, and antiviral pharmacological effects. Its complex chemical structure and multi-target mechanism of action provide new strategies for treating various diseases. Despite limitations in water solubility and bioavailability, nomirin still demonstrates good druggability and safety.
In the future, through pharmaceutical improvements, structural optimization, and in-depth mechanistic research, nomirin is expected to become an important candidate for natural product drug development, contributing new drug resources for the treatment of metabolic diseases, tumors, and inflammatory diseases. Ongoing basic and clinical research will drive Nomirin from the laboratory to clinical applications, opening a new chapter in the development of natural product drugs.
Shenshuai
Wenjing
Hedandan
