Product name: Gamma-mangostin
Synonym name: Normangostin
Catalogue No.: BP0614
Cas No.: 31271-07-5
Formula: C₂₃H₂₄O₆
Mol Weight: 396.439
Botanical Source: Garcinia mangostana L.
Physical Description:
Type of Compound: Xanthones

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:

gamma-Mangostin is a dual agonist that activates both PPARδ and PPARα, is also a novel competitive antagonist for the 5-HT2A receptors in vascular smooth muscles and platelets.gamma-Mangostin has free radical scavenging activity, and antiproliferative and apoptotic activity in HepG2 cells, and exhibits antihypertensive, anti-inflammatory, analgesic effects. gamma-Mangostin could as a preventive agent of the metabolic syndrome, and could serve as a micronutrient for colon cancer prevention.

References:

BMC Complement Altern Med. 2013 Jul 19;13:182.    

Antileptospiral activity of xanthones from Garcinia mangostana and synergy of gamma-mangostin with penicillin G.   

Leptospirosis, one of the most widespread zoonotic infectious diseases worldwide, is caused by spirochetes bacteria of the genus Leptospira. The present study examined inhibitory activity of purified xanthones and crude extracts from Garcinia mangostana against both non-pathogenic and pathogenic leptospira. Synergy between gamma-Mangostinand penicillin G against leptospires was also determined. 

METHODS AND RESULTS:

Minimal inhibitory concentrations (MIC) of crude extracts and purified xanthones from G. mangostana and penicillin G for a non-pathogenic (L. biflexa serovar Patoc) and pathogenic (L. interrogans serovar Bataviae, Autumnalis, Javanica and Saigon) leptospires were determined by using broth microdilution method and alamar blue. The synergy was evaluated by calculating the fractional inhibitory concentration (FIC) index. The results of broth microdilution test demonstrated that the crude extract and purified xanthones from mangosteen possessed antileptospiral activities. The crude extracts were active against all five serovars of test leptospira with MICs ranging from 200 to ≥ 800 μg/ml. Among the crude extracts and purified xanthones, garcinone C was the most active compound against both of pathogenic (MIC =100 μg/ml) and non-pathogenic leptospira (MIC = 200 μg/ml). However, these MIC values were higher than those of traditional antibiotics. Combinations of gamma-Mangostin with penicillin G generated synergistic effect against L. interrogans serovars Bataviae, Autumnalis and Javanica (FIC = 0.52, 0.50, and 0.04, respectively) and no interaction against L. biflexa serovar Patoc (FIC =0.75). However, antagonistic activity (FIC = 4.03) was observed in L. interrogans serovar Saigon. 

CONCLUSIONS:

Crude extracts and purified xanthones from fruit pericarp of G. mangostana with significant antibacterial activity may be used to control leptospirosis. The combination of xanthone with antibiotic enhances the antileptospiral efficacy.    

J Pharm Pharmacol. 2013 Sep;65(9):1419-28.    

Antitumour and free radical scavenging effects of γ-mangostin isolated from Garcinia mangostana pericarps against hepatocellular carcinoma cell.   

Liver cancer is one of the highest rate diseases in southeastern Asia. Recently, many of functional foods and alternative medicines are very popularly utilized to prevent chronic diseases and cancer in Taiwan. In this study, we wanted to select and develop some of novel effectual agents or phytochemicals of gamma-Mangostin for clinical management or prevent hepatocellular carcinoma cell (HCC). 

METHODS AND RESULTS:

Lipid peroxidation (LPO) is an autocatalytic mechanism which induced tissue injure and carcinogenesis. In this study, the inhibitory activity of gamma-Mangostin on oxidative damage induced rat mitochondria LPO, the free radical scavenging of gamma-Mangostin and the apoptotic effects of gamma-Mangostin on HepG2 cells were investigated. gamma-Mangostin processed activity to inhibit LPO and scavenge 2,2-diphenyl-1-picrylhydrazyl. gamma-Mangostin showed antiproliferative activity and induced nuclear condensation and apoptotic bodies appearance under Giemsa staining by microscopic observation. In addition, gamma-Mangostin showed increases of hypodiploid cells via propidium iodide, 2'7'-dichlorofluorescein diacetate, and 3,3'-dihexyloxacarbocyanine iodide staining by flow cytometry analysis in HepG2 cells. 

CONCLUSIONS:

gamma-Mangostin has demonstrated free radical scavenging activity, and antiproliferative and apoptotic activity in HepG2 cells. The proof suggests that gamma-Mangostin is a lead compound candidate for clinical management or prevent HCC.    

J Med Assoc Thai. 2012 Dec;95 Suppl 12:S63-8.    

Mechanisms of vasorelaxation to gamma-mangostin in the rat aorta.    

To investigate the effects of gamma-Mangostin on vascular tone and its mechanisms in the isolated rat aorta. 

METHODS AND RESULTS:

Aortic rings from male Wistar rats were precontracted with methoxamine. Changes in tension were measured using an isometric force transducer and recorded on the MacLab recording system. Vasorelaxant effects of gamma-Mangostin were studied in the presence of 300 microM N(G)-nitro L-arginine methyl ester (L-NAME), 10 microM 1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ), 10 microM indomethacin, 60 mM KCl, 5 mM tetraethylammonium (TEA), 10 microM glibenclamide, 1 mM4-aminopyridine (4-AP) or 30 microM barium chloride (BaCl2). Moreover the effects of gamma-Mangostin on contraction to CaCl2 were evaluated. gamma-Mangostin (1-100 microM) induced a concentration-dependent vasorelaxation in rat aortic rings precontracted with methoxamine. This effect was significantly reduced after removal of the endothelium and after pretreatment of the rings with L-NAME, ODQ, high KCl solution, or TEA. However, vasorelaxant responses to gamma-Mangostin were not altered by indomethacin, 4-AP, BaCl2 or glibenclamide. Moreover, contractions to CaCl2 (10 mM-30 mM) were reduced by pre-treatment with gamma-Mangostin (10 and 100 microM). 

CONCLUSIONS:

gamma-Mangostin causes vasorelaxation which is mediated via the NO-cGMP pathway. Moreover activation of K+ channels and inhibition of extracellular Ca2+ influx from the extracellular space are largely involved in the relaxant effects of gamma-Mangostin. These data suggest that gamma-Mangostin may acts as an antihypertensive agent.    

Pharmacol Biochem Behav. 2010 Apr;95(2):166-72.    

New medicinal properties of mangostins: analgesic activity and pharmacological characterization of active ingredients from the fruit hull of Garcinia mangostana L.   

The fruit hull of Garcinia mangostana L. contains oxygenated and prenylated phenol derivatives, such as xanthones or xanthen-9H-ones, and is used by people in Southeast Asia as a traditional medicine for the treatment of abdominal pain, dysentery, wound infections, suppuration, and chronic ulcer. We isolated the active ingredients from the crude ethanol extract of G.mangostana L. (CEM) and investigated their analgesic effects and underlying mechanisms. 

METHODS AND RESULTS:

CEM at intragastric (i.g.) doses of 0.5, 1, and 3 g/kg clearly exhibited antinociceptive effects in the hot-plate and acetic acid-induced writhing tests in mice. Two isolated compounds, alpha-mangostin and gamma-Mangostin, exhibited analgesic effects at doses of 25 and 50 mg/kg (i.g.) in the hot-plate and formalin tests, respectively. CEM at doses of 0.5, 1, and 3 g/kg significantly inhibited xylene-induced release of inflammatory mediators. CEM, alpha-mangostin, and gamma-Mangostin each dose-dependently demonstrated the ability to scavenge reactive oxygen species. 

CONCLUSIONS:

In conclusion, our results demonstrate that CEM and mangostins possess potent peripheral and central antinociceptive effects in mice and suggest that xanthones may be developed as novel analgesics and anti-inflammatory drugs.    

HPLC of Gamma-mangostin

HNMR of Gamma-mangostin

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Natural products have long been an important treasure trove for innovative drug discovery, among which polyphenolic compounds have attracted much attention due to their wide range of biological activities. Gamma mangostin (CAS number: 31271-07-5), as a structurally unique natural product of anthraquinone, has emerged in the field of pharmacology research in recent years. Initially, research focused on the antioxidant and antibacterial properties of the skin of the source plant Garcinia mangostana L. However, as research deepens, scientists have discovered that γ - quercetin exhibits complex pharmacological activities far beyond traditional understanding, with multiple targets and pathways. It has been identified as a novel competitive 5-HT2A receptor antagonist and potent COX-2 inhibitor, while also effectively inhibiting the pathological fibrosis process of transthyretin (TTR). In addition, its potential in anti-inflammatory, antibacterial, antioxidant, anti-cancer, especially in regulating glucose and lipid metabolism disorders (such as diabetes, obesity) makes it an attractive candidate molecule in the research and development of therapeutic drugs for metabolic diseases. This article aims to provide a systematic review of the chemical properties, plant sources, pharmacological activities, molecular mechanisms of action, pharmacological evaluation, and clinical application prospects of γ - quercetin, in order to provide comprehensive scientific references for the in-depth research and development of this compound.

Chemical structure and physicochemical properties

Gamma spinosin is a tetraoxo substituted anthraquinone derivative with a molecular formula of C23H24O6 and a molecular weight of 396.4390. Its core structure is an anthraquinone core, which undergoes characteristic substitutions at positions 1, 3, 6, and 7: a hydroxyl group (- OH) is attached to positions 1 and 3, a methoxy group (- OCH3) is attached to position 6, and an isoprene side chain (- C5H9) is attached to position 7. This unique isopentenyl structure is considered a key chemical basis for its excellent lipid solubility and diverse biological activities.

Its physicochemical properties profoundly affect its bioavailability and pharmacological effects. The calculated lipid water partition coefficient (LogP) is 4.5374, indicating that the compound has a high degree of lipophilicity. Consistent with this, its water solubility is extremely low, only 0.0196 mg/mL, indicating that its absorption and distribution in vivo may face challenges. The topological polar surface area (TPSA) of the molecule is 111.13 Å ², reflecting the presence of multiple polar functional groups (hydroxyl, carbonyl). In the preliminary safety screening, the Ames test result of γ - spinosad was 0.6 (usually considered a potential mutagenic risk of>1.5), indicating that it has no significant mutagenicity in this testing system. Meanwhile, it does not inhibit hERG potassium ion channels, indicating a lower risk of causing prolonged QT interval in the heart. However, its blood-brain barrier permeability is predicted to be "low", which means it may be difficult for it to enter the central nervous system and exert direct effects. These physicochemical and pharmacological parameters provide clear directions for the subsequent development of formulations and structural optimization.

Plant sources and extraction methods

The main source of γ - rennin is the fruit peel of the Garcinia mangostana L. plant in the family Theaceae. Mangkhut peel is commonly used in traditional medicine to treat diarrhea, infections, wound healing, and inflammation, and its abundant anthraquinone components are the material basis of its pharmacological effects. In addition to γ - quercetin, the skin of mangosteen also contains various structurally similar anthraquinone compounds such as α - quercetin, β - quercetin, and garcinone E, which together form its complex biological activity spectrum.

Efficient extraction and separation of γ - quercetin from plant materials is a prerequisite for studying its activity. The conventional extraction methods include:
1. Solvent extraction method The most commonly used method is to extract, reflux or ultrasound assisted extraction of dried mangosteen peel powder using methanol, ethanol, acetone or their aqueous solutions. Due to the high lipophilicity of γ - cyclodextrin, high proportion organic solvents have better extraction efficiency.
2. Chromatographic separation method The crude extract is further separated and purified by silica gel column chromatography, preparative thin-layer chromatography, or high-performance liquid chromatography (HPLC). Reverse phase HPLC (such as C18 column) has become the gold standard method for obtaining high-purity γ - quercetin (for standard or in-depth research) due to its high resolution.
3. Modern extraction techniques Technologies such as supercritical CO2 extraction and microwave-assisted extraction have also been explored to improve extraction efficiency and selectivity, while reducing the use of organic solvents.

The optimization of extraction processes usually focuses on factors such as solvent type, concentration, temperature, time, and solid-liquid ratio to maximize the yield of the target compound.

Pharmacological activity research

A large number of in vitro and in vivo studies have confirmed that γ - quercetin has broad and significant pharmacological activities.

1. Anti inflammatory and analgesic activity Gamma spinosad is an effective COX-2 inhibitor that selectively inhibits the production of inflammatory mediators such as prostaglandin E2. It exhibits strong anti-inflammatory effects in various animal inflammation models, such as carrageenan induced paw swelling in rats and cotton ball induced internal bud swelling. It may also contribute to its analgesic effect by inhibiting the dual pathways of COX-2 and 5-HT2A receptors.
2. Antibacterial and antioxidant activity It exhibits inhibitory activity against various Gram positive bacteria (such as Staphylococcus aureus, Bacillus subtilis) and some fungi. Its antioxidant capacity originates from its phenolic hydroxyl structure, which can effectively scavenge free radicals such as DPPH and ABTS, inhibit lipid peroxidation, and protect cells from oxidative stress damage.
3. anticancer activity: Studies have shown that γ - troponin can inhibit the proliferation and promote apoptosis of many cancer cell lines (such as breast cancer, colon cancer, liver cancer, leukemia). Its mechanism involves inducing cell cycle arrest, activating caspase cascade reactions, regulating Bcl-2 family proteins, and inhibiting survival promoting signaling pathways such as NF - κ B.
4. Metabolic regulatory activity (emphasis)：
   • anti-diabetic Gamma spinosad can improve insulin resistance and promote the uptake and utilization of glucose by peripheral tissues. In the animal model of diabetes, it can effectively reduce fasting blood glucose, improve glucose tolerance, and alleviate kidney and liver complications related to diabetes.
   • Anti obesity This is one of its most promising activities. In animal models of nutritional obesity, gamma lipocalin can significantly reduce body weight, decrease white adipose tissue accumulation, and improve lipid abnormalities (lowering triglycerides, total cholesterol, and low-density lipoprotein cholesterol). Its function is closely related to inhibiting fat production, promoting fat breakdown, and energy expenditure.

Mechanism of action and molecular targets

The pleiotropic pharmacological effects of γ - quercetin stem from its regulation of multiple key molecular targets.

1. Core target：

   • 5-HT2A receptor antagonist Competitive antagonism of 5-HT2A receptor with extremely high affinity (IC50=3.5 nM). This receptor plays an important role in vascular constriction, platelet aggregation, emotional regulation, and metabolic control. Its antagonistic effect can explain some of its cardiovascular protection (such as reducing the perfusion pressure response of coronary arteries to 5-HT, IC50=0.32 µ M) and potential anti anxiety and anti depression effects.
   • cox-2 inhibitors The core mechanism of its anti-inflammatory effect is to directly inhibit COX-2 enzyme activity and reduce the synthesis of pro-inflammatory prostaglandins.
   • TTR stabilizer Binding to the binding site of thyroxine (T4) stabilizes the TTR tetramer structure, preventing its dissociation and misfolding to form amyloid fibers. This provides a theoretical basis for its application in the treatment of TTR amyloidosis, such as familial amyloidosis and cardiomyopathy.

2. Anti obesity related target network：
   Gamma reversed spinosad regulates energy metabolism and fat homeostasis through a complex network, and its targets include:

   • Transcription regulatory factors: Inhibition PPARγ(Peroxisome proliferator activated receptor gamma) and SREBP-1c Activity and expression of sterol regulatory element binding protein-1c. PPAR γ is the main regulatory factor for adipocyte differentiation and lipid storage; SREBP-1c drives fatty acid and triglyceride synthase (such as FASN Expression of fatty acid synthase. Inhibiting these two pathways can fundamentally reduce fat production.
   • Adipose factors and receptors Regulating hormones secreted by adipose tissue. It may increase Adiponectin (ADIPOQ)The expression of (improving insulin sensitivity) and its impact Leptin (LEP)And its receptors（LEPR）Signal transduction to enhance satiety. Meanwhile, it may have an impact POMC (POMC)Neuronal activity promotes anorexia signals.
   • Energy consumption and lipolysis related proteins: Promote UCP1 The expression of uncoupling protein 1, which is present in brown/beige adipose tissue, can release chemical energy in the form of heat energy, increasing energy consumption. In addition, by acting onβ 3-adrenergic receptor (ADRB3)May stimulate fat breakdown. inhibit FABP4 Fatty acid binding protein 4 can reduce the transport and storage of fatty acids within adipocytes.
   • Inflammation and oxidative stress pathway Its anti-inflammatory (inhibiting COX-2, NF - κ B) and antioxidant effects help alleviate chronic low-grade inflammation and oxidative stress associated with obesity, which are key factors leading to insulin resistance and metabolic syndrome.

In summary, gamma rennin exerts its anti obesity and metabolic disorder improving effects through multi-target synergistic effects, including inhibiting fat synthesis, promoting fat breakdown and oxidation, increasing energy consumption, improving insulin sensitivity, and alleviating metabolic inflammation.

Evaluation of drug properties and pharmacokinetics

Despite its excellent pharmacological activity, the development of the pharmacological properties of γ - quercetin still faces challenges, which is currently the focus of research.

1. Absorption, distribution, metabolism, excretion (ADME)：

   • absorb High LogP and low water solubility may result in poor oral bioavailability. Studies have shown that its absorption in the intestine may be limited by solubility and permeability. Formulation technologies such as nanocrystals, solid dispersions, and liposomes are effective strategies for improving oral absorption.
   • distribution Lipophilia makes it easy to distribute to tissues such as fat and liver, but the blood-brain barrier has low permeability, limiting its direct action.
   • Metabolism As a polyphenolic compound, γ - quercetin may undergo extensive phase I (such as hydroxylation, demethylation) and phase II (glucuronidation, sulfation) metabolism in the body. The liver and intestines are the main metabolic sites. Its isopentenyl side chain may be one of the metabolic modification sites.
   • excretion Metabolites are mainly excreted through urine and bile.

2. Challenges and optimization of drug development：

   • Solubility and permeability This is the main bottleneck. Improvements need to be made through medicinal chemistry (preparation of water-soluble prodrugs such as phosphate esters and amino acid esters) or pharmacy (advanced delivery systems) methods.
   • Metabolic stability Evaluate its metabolic rate in liver microsomes or liver cells, and if necessary, modify the easily metabolized sites to increase half-life.
   • safety Although the initial risks of genetic toxicity (Ames) and cardiac toxicity (hERG) are low, a comprehensive preclinical safety evaluation is still needed, including acute toxicity, chronic toxicity, reproductive toxicity, etc.
   • Drug drug interactions It is necessary to investigate whether it is a substrate, inhibitor, or inducer of CYP450 enzymes (such as CYP3A4) to assess potential interaction risks.

Clinical application prospects and prospects

The multi-target action characteristics of γ - quercetin have depicted broad prospects for its application in various disease fields.

1. Potential therapeutic areas：

   • Metabolic diseases: As a candidate drug or functional food ingredient for anti obesity and anti type 2 diabetes. It may have advantages over single target drugs by regulating multiple mechanisms of fat production, energy metabolism, and inflammation, especially for complex obesity accompanied by inflammation.
   • cardiovascular disease Its 5-HT2A receptor antagonistic and anti-inflammatory properties may have therapeutic potential for atherosclerosis, hypertension, coronary spasm and other diseases.
   • Neurodegenerative diseases The stabilizing effect of TTR makes it a potential drug for treating TTR amyloidosis. In addition, its anti-inflammatory and antioxidant properties may also have neuroprotective implications for diseases such as Alzheimer's and Parkinson's (although BBB permeability is a major challenge).
   • Inflammatory diseases and cancer adjuvant therapy Can be used to treat chronic inflammations such as arthritis and colitis. Its anti-cancer activity also makes it possible to serve as an adjuvant or sensitizer for chemotherapy.

2. Future research directions：

   • In depth mechanism exploration Using omics techniques (proteomics, metabolomics) to comprehensively reveal its functional network and discover new signaling pathways and biomarkers.
   • Structural optimization and development of analogues Based on its pharmacophore, conduct systematic structure-activity relationship research, design and synthesize derivatives or analogues with better solubility, metabolic stability, and target selectivity.
   • Advanced delivery system research and development Vigorously develop nano formulations and targeted formulations (such as adipose tissue targeting) targeting their physical and chemical defects to improve efficacy, reduce dosage and side effects.
   • Advance preclinical and clinical research Conduct Good Laboratory Practice (GLP) toxicology studies that comply with regulations, and design rigorous clinical trials to verify their safety, pharmacokinetic characteristics, and effectiveness for specific indications such as non-alcoholic fatty liver disease and obesity in humans.
   • Multi component collaborative research Explore the synergistic effects of γ - quercetin in combination with other natural products or existing drugs, and develop compound therapies.

Conclusion

As a natural anthraquinone derived from mangosteen, γ - spinosad has transformed from a traditional phytochemical into a modern pharmacological star molecule with a clear multi-target mechanism of action. Its outstanding abilities in 5-HT2A receptor antagonism, COX-2 inhibition, TTR stabilization, and regulation of key metabolic pathways such as PPAR γ/SREBP-1c have laid a solid scientific foundation for its application in anti-inflammatory, anti metabolic disease, neuroprotection, and anti-cancer fields. Although its inherent low water solubility and potential pharmacokinetic defects are practical obstacles to clinical application, they provide valuable topics for pharmaceutical chemistry, pharmacy, and translational medicine research. Through continuous in-depth mechanism research, rational structural optimization and innovative preparation development, γ - leptosporin and its derivatives are expected to become new drugs for treating a series of major chronic diseases such as obesity, diabetes and its complications in the future, fully demonstrating the lasting vitality and great potential of natural products in the development of innovative drugs.