1.1 Garcinia mangostana: Botanical basics and its role in traditional medicine

Commonly called “queen of the fruits”, the mangosteen or Garcinia mangostana (G. mangostana) is a plant of the Clusiaceae family, primarily cultivated in countries of Southeast Asia like Indonesia, Myanmar, Malaysia, the Philippines, and Thailand [1, 2]. The mangosteen fruit itself has a spherical shape and changes its colour from green to purple during maturation [3] (Fig. 1). While the pulp is edible and enjoyed for its sweet taste, around 60% of the total fruit mass constitutes the inedible pericarp, accounting for 30.8 million tons of global waste per year [4, 5].

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“Flowers and Fruit of the Mangosteen, and a Singapore Monkey” by Marianne North (1830–1890)

Image courtesy of The Board of Trustees of the Royal Botanic Gardens, Kew

Citation: European Journal of Microbiology and Immunology 2025; 10.1556/1886.2025.00006

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Both Chinese medicine and ayurveda value G. mangostana for its health-promoting benefits [6]. Traditional Thai medicine makes use of the mangosteen as a phytopharmaceutical agent in the treatment of a multitude of health problems, including but not limited to abdominal pain, diarrhea, arthritis, fever, eczema, wounds, and skin infections [6]. Also, the mangosteen is used for digestive and energetic teas in certain parts of South America [7]. Some people of African countries apply the leaves and bark of G. mangostana as means of oral care [8].

1.2 Current state of research and perspectives for clinical use

Mangosteen extracts contain compounds with biological activities such as xanthones, flavonoids, and terpenoids [9, 10]. Xanthones are a class of polyphenols, belonging to the secondary plant metabolites [11, 12]. In particular, prenylated xanthones are derived from the pericarp, whole fruit, bark, and leaves of G. mangostana [13]. At least 68 mangosteen xanthones, including α-mangostin, have been described, entailing a plethora of beneficial properties [13].

Respective compounds demonstrated the following effects, among others: anti-oxidant, anti-inflammatory, anti-viral, anti-fungal, anti-parasitic including anti-malarial, anti-allergic, and anti-proliferative [6, 14, 15]. Since multi-drug resistant bacteria are on the rise [16], adjunct or standalone therapeutic options besides common synthetic antibiotics are in great demand, warranting research on the anti-bacterial capacity of the mangosteen and compounds like α-mangostin.

1.3 Objective

With the review at hand we intend to shed light on the potential of the mangosteen fruit and its compounds to be probed as novel agents against bacterial infections in humans. In line with this, we appreciated any publication giving an account of relevant effects, mechanisms, experimental experience, and safety aspects.

2.1 Inclusion and exclusion criteria

Striving for a comprehensive overview, we imposed no restrictions on the publication dates; nevertheless, only original articles in English were considered. While we included publications from the field of human including dental medicine, we excluded all publications with a focus on veterinary medicine, biotechnology, or from any other insufficiently relevant perspective. All studies dealing with the anti-bacterial capacity of the mangosteen fruit in a broader sense, involving both in vitro and in vivo experiments, were embraced.

2.2 Search strategy and data retrieval

An initial search for pertinent literature was conducted on the 18th of November, 2024. However, the final selection of literature was based on a search from the 8th of January, 2025. Making use of the search engine “PubMed”, which accesses the MEDLINE database, led us to 62 results. The search terms entered as well as the tags and Boolean operators set in PubMed's “Advanced Search Builder” are shown in Fig. 2. Applying the earlier described criteria to a screening of the identified literature, we had to exclude a total of 37 publications. Notably, two potentially suitable articles could not be included due to their unavailability. The remaining 23 studies constituted the literature basis of this review.

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Screenshot (abridged and adapted) of “History and Search Details” in PubMed's Advanced Search Builder on the 8th of January, 2025

Citation: European Journal of Microbiology and Immunology 2025; 10.1556/1886.2025.00006

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3.1 Compounds, chemistry, and conditions

Chomnawang et al. screened 17 Thai medicinal plants, including G. mangostana, for anti-bacterial capacity against methicillin-resistant Staphylococcus aureus (MRSA) [17]. Both the Staphylococcus aureus (S. aureus) strain ATCC 25923 and MRSA were inhibited by crude extract, as zones of inhibitions measuring 11.3 ± 0.60 mm and 10.00 ± 0.00 mm indicated, respectively. For 16 MRSA isolates, G. mangostana required a minimum inhibitory concentration (MIC) value of only 39 μg mL⁻¹, however, one MRSA isolate entailed a MIC value of up to 1,250 μg mL⁻¹. In terms of α-mangostin against MRSA, MIC and minimum bactericidal concentration (MBC) values of 1.95 and 3.91 μg mL⁻¹ were identified, respectively. Hence, extracts of G. mangostana and α-mangostin alone were considered therapeutic options for resistant strains of S. aureus [17].

Liu et al. studied the suitability of α-mangostin derived from mangosteen peel as an alternative treatment for enteric infections caused by Clostridium perfringens (C. perfringens) [18]. In particular, the MIC of α-mangostin employed against five genotypes of C. perfringens was 0.5 μg mL⁻¹, portending an anti-bacterial superiority over common antibiotics like tilmicosin or lincomycin in livestock and poultry suffering from C. perfringens. Even in experiments with up to 79 different bacterial isolates, the MIC of α-mangostin remained at 0.5 μg mL⁻¹, whereas the antibiotic tylosin showed MIC₅₀ and MIC₉₀ values of 1 μg mL⁻¹ and 4 μg mL⁻¹, respectively. Furthermore, α-mangostin maintained its anti-bacterial efficacy against pathogens like MRSA and vancomycin-resistant Enterococcus species (VRE) even under anaerobic conditions, supporting the xanthone's prospect of in vivo use. The activity of the isolated xanthone appears to be affected by prenylation, as structure-activity relationship analysis indicated. While a hydroxyl group at C3 on the parent ring structure entailed improved anti-bacterial activity, a diminished efficacy was ascribed to a methoxyl group at C7. The activity of α-mangostin was not impeded by pretreatment with temperatures from −20 °C to 37 °C for one hour; neither had pH values of 3.8–7.4 a substantial influence on α-mangostin. On a related note, α-mangostin exhibited similar activity even when incubated in a simulated setting of gastric and intestinal fluids. Experiments with rats as well as mice demonstrated that the median lethal dose of α-mangostin amounted to more than 1,000 mg kg⁻¹, indicating low toxicity. With doses of 4, 8, and 20 mg per kg body weight, α-mangostin was tested in a broiler chicken model of necrotic clostridial enteritis. Adding α-mangostin to the nourishment promoted the gut microbiome through a diminished presence of clostridia. Also, an increased mucin expression was observed, resulting in an enhanced intestinal barrier [18].

Experiments of Palkar et al. addressed the chemical properties of degraded α-mangostin from G. mangostana and their relevance for anti-bacterial activity [19]. Analyses of nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry led to the identification of structural modifications following acid exposure, i. e. the degraded α-mangostin featured changes of two prenyl groups at the C2 and C8 position. Depending on the acidic condition, the degree of degradation ranged from 14.1% up to 78.4% at 0.1 N HCl and 2 N HCl, each for an hour. As a consequence of 3 N HCl at 80 °C for eight hours, α-mangostin transformed into another compound with a differing structure. Under the influence of varying temperature and humidity as well as UV light, oxidative, and alkaline exposure, only negligible effects on α-mangostin were noted, portending pronounced stability. MIC values ranging from 0.39 up to 1.56 μg mL⁻¹ were determined for α-mangostin, whereas degraded α-mangostin had MIC values above 25 μg mL⁻¹. However, the degraded formation was still capable of binding with glucosyltransferase-SI, originating from Streptococcus mutans (S. mutans) and human acetylcholinesterase, basically like non-degraded α-mangostin did in molecular docking simulations. Hence, the authors concluded that even acidic influence causing degradation does not entirely abolish the anti-bacterial efficacy of α-mangostin, indicating the demand for further research on a stress resistant and generally stable phytopharmaceutical formulation [19].

Albuquerque et al. surveyed the chemical composition of compounds found in mangosteen pericarp, seeking also insights related to their anti-bacterial efficacy [20]. The use of hydroethanolic, ethanolic, and aqueous extracts led to the detection of seven organic acids, three tocopherol isomers, four fatty acids, and fifteen phenolic compounds. All of the tested extracts exhibited in vitro anti-bacterial effects, with the hydroethanolic and ethanolic extracts being superior to the aqueous one. However, the ethanolic extract appeared to have bactericidal potential. Concretely, both Gram-negative and Gram-positive bacterial growth was inhibited by the mangosteen pericarp extracts, including but not limited to Escherichia coli (E. coli), Klebsiella pneumoniae, Enterococcus faecalis, Listeria monocytogenes, and MRSA. The sole exception was Pseudomonas aeruginosa, whose growth was not affected by pericarp extracts at the highest examined concentration of 20 mg mL⁻¹. In general, the observed anti-bacterial effects were never bactericidal, only bacterial growth inhibition was achieved. While the growth of Gram-positive bacteria was impeded already at concentrations of 0.625 up to 1.25 mg mL⁻¹, the inhibition of Gram-negative bacteria required concentrations of 2.5 up to 10 mg mL⁻¹. Given the overall promising results, mangosteen pericarp extracts were assigned pharmaceutical potential [20].

Dharmaratne et al. investigated the anti-bacterial effects and chemistry of xanthones isolated from G. mangostana and synthetic analogues [21]. For instance, γ-mangostin had a MIC value of 6.25 μg mL⁻¹ when tested against methicillin-sensitive S. aureus (MSSA), both VRE and vancomycin-sensitive Enterococcus; against MRSA the MIC of γ-mangostin numbered 3.13 μg mL⁻¹. These results were similar to the anti-bacterial efficacy of the antibiotic gentamicin, which was used as the positive control. Further experiments with MRSA and VRE strains were carried out on compounds including but not limited to: α-mangostin, β-mangostin, γ-mangostin, 3,6,7-trimethoxy-γ-mangostin, synthetic analogues of γ-mangostin, and 6-methoxy-γ-mangostin. The strongest anti-bacterial capacity was found in terms of α-mangostin and γ-mangostin, whereas 6-methoxy-γ-mangostin had no growth-inhibiting effect on the tested pathogens. Following the analysis of bioassay results, it was concluded that a strong anti-bacterial capacity of 1,3,6,7-tetraoxygenated xanthones derived from G. mangostana depends on the combination of C-6 and C-3 hydroxyl groups as well as a prenyl side chain at C-2 [21].

Wang et al. published their research findings on the anti-bacterial capacity of a novel compound derived from the bark of G. mangostana, called garmoxanthone, in addition to ten known xanthones [22]. Involving MIC values of 3.9 μg mL⁻¹ each, the xanthone demonstrated pronounced inhibitive activity against MRSA ATCC 43300 and MRSA CGMCC 1.12409. For the three tested Vibrio strains (namely, Vibrio vulnificus, Vibrio rotiferianus, and Vibrio campbellii), MIC values from 15.6 to 31.2 μg mL⁻¹ were ascertained. Aside from that, isogarcinol, garcinone E, and dulxanthone A also exhibited anti-bacterial effects against MRSA and Vibrio strains, as indicated by MIC values ranging from 3.9 to 62.4 μg mL⁻¹. However, the other isolated compounds showed if at all, rather negligible efficacy; that pertained to mangostanol, 3-isomangostin hydrate, 9-hydroxycalabaxanthone, br-xanthone, gartanin, 8-deoxygartanin, and nigrolineaxanthone T. Although its chemical structure was inferred from spectroscopic data and garmoxanthone itself was extensively analzyed, the authors accentuated the necessity for studies on the relations among structure and activity as well as toxicity. However, garmoxanthone was regarded as a potential therapeutic option for infections with MRSA as causative agent [22].

Munar-Bestard et al. conducted an in vitro experiment with a xanthone from G. mangostana called mangostanin [23]. Considering its suitability for the use on skin and oral tissues, the authors tested the xanthone against a variety of clinically relevant bacteria. Killing more than 80% of the present pathogens required mangostanin concentrations of 0.002% and 0.001% in case of Porphyromonas gingivalis (P. gingivalis) as well as S. mutans, S. aureus, and Staphylococcus epidermidis (S. epidermidis), respectively. The same result was achieved for Streptococcus pyogenes and Cutibacterium acnes (C. acnes) with a mangostanin concentration of only 0.0002%, being comparable to the effect of antiseptics like chlorhexidine (at 0.001% concentration). In an additional experiment, saliva from healthy donors was spread out on glass slides to evaluate anti-biofilm capacities. In fact, the application of 0.05% mangostanin and 0.2% chlorhexidine led each time to a similar inhibition of plaque development. Employing the lactate dehydrogenase assay as a measurement tool for cytotoxicity, 0.001% chlorhexidine showed 100% cytotoxicity, whereas mangostanin concentrations of up to 0.002% exhibited good biocompatibility with gingival fibroblasts. Also, 0.002% mangostanin had nearly no effect on metabolic activity of gingival fibroblasts in contrast to 0.001% chlorhexidine, which induced a substantial reduction. Lastly, 0.05% mangostanin was tested as a component of hyaluronic acid hydrogels for use against S. aureus on skin and P. gingivalis on periodontal mucosa, revealing strong anti-bacterial activity in respective tissue models. On a related note, both a cytotoxicity (MTT) assay and histological examinations underlined good biocompatibility. Given the promising results of their experiments, the authors highlighted the potential suitability of mangostanin as a candidate for novel formulations and emphasized partial superiority over established antiseptics [23].

3.2 Phytopharmaceutical mixtures

Pasaribu et al. surveyed the anti-bacterial efficacy of mangosteen pericarp extract both in comparison to and in combination with other phytotherapeutic substances [24]. Using the Folin-Ciocalteu method, it was shown that the pericarp extract contained comparably high levels of phenol (12.09%) and tannin (9.85%), whereas also saponin (34.19%) was detected. Tested against E. coli, the antibiotic chloramphenicol 18 ppm (inhibition zone of 13.75 mm) still possessed a higher anti-bacterial effect than 100% mangosteen extract (inhibition zone of 11.75 mm). Beginning with a concentration of 50%, mangosteen pericarp extract achieved an inhibition zone against E. coli of at least 9.75 mm. However, already a 25–50% concentrated combination (termed “COMBI”) of mangosteen pericarp extract with Cocos nucifera shell liquid smoke and clove leaf extract was roughly as potent as chloramphenicol, presenting a dose-dependent effect. A COMBI concentration as low as 6.25% was capable of bacterial inhibition with an inhibition zone measuring 6.71 mm. The largest clear zone was reached when 100% COMBI was applied against E. coli, resulting in 19.50 mm. Of note, the zones of inhibition accomplished by C. nucifera shell liquid smoke alone were greater than those of COMBI, suggesting that, in fact, mangosteen pericarp extract reduced the overall efficacy of COMBI. Nevertheless, the exclusive use and the described combination were deemed agents with potential as a treatment for bacterial infections [24].

Chusri et al. analyzed the anti-bacterial activity of various Thai herbal formulas, including THR-SK010, as a wound treatment [25]. In addition to a mangosteen pericarp extract, THR-SK010 also comprised components from Curcuma longa, Areca catechu, and Oryza sativa. The ethanolic extract demonstrated pronounced potency against each twenty MRSA and MSSA isolates, as indicated by a MIC₉₀ value of 4 and 8 μg mL⁻¹, respectively. This anti-bacterial activity extended also to the S. aureus strain ATCC 29213 (MIC value of 4 μg mL⁻¹). However, the water extract did not exhibit sufficient anti-staphylococcal efficacy, since the MIC measured 250–1,000 μg mL⁻¹. After the application of ethanolic THR-SK010 at concentrations of one up to eight times MIC for two hours, a reduction in viable MRSA bacteria by 1.3–2.3 log colony-forming units (CFU) per mL was noted. A reduction in viable bacteria by 3.8–7.7 and 2.0–6.3 log CFU per mL was determined in terms of S. aureus ATCC 29213 and MSSA isolate at 18 hours post treatment. However, the mangosteen formula was associated with some cytotoxicity in tests on a Vero cell line. Nevertheless, the potential of the formula THR-SK010 as a phytopharmaceutical treatment option for wound infections was reinforced by the experimental results, prompting future studies on in vivo activity [25].

3.3 G. mangostana in combination with antibiotics

Iinuma et al. concisely described their results of experiments on the anti-staphylococcal capacity of xanthones isolated from G. mangostana [26]. Employed against MSSA and MRSA strains, MIC values of α-mangostin from a benzene extract of mangosteen pericarps numbered 1.57–12.5 μg mL⁻¹. Combined with the antibiotic vancomycin, a synergistically improved effect was observed. Besides, the respective extract had a MIC of 80 μg mL⁻¹ against the S. aureus strain NIHJ 209p. In view of these in vitro results, the authors attested to the distinct potency of xanthones from G. mangostana in the treatment of staphylococcal infections [26].

Sakagami et al. conducted a study on the treatment of VRE with α-mangostin alone as well as together with antibiotics [27]. Originating in the stem bark of G. mangostana, α-mangostin was capable of bacterial inhibition against five strains of VRE and nine strains of MRSA, as respective MIC values of 3.13–6.25 μg mL⁻¹ and 6.25–12.5 μg mL⁻¹ demonstrated. Synergistic activity was observed in the combination of α-mangostin and gentamicin against VRE as well as α-mangostin and vancomycin hydrochloride against MRSA with fraction inhibitory concentration (FIC) indices of 0.451 ± 0.069 and 0.441 ± 0.131, respectively. Moreover, partial synergism of α-mangostin with other antibiotics like ampicillin (0.606 ± 0.328), minocycline (0.969 ± 0.217), and fosfomycin (0.826 ± 0.286) against VRE was noted. Synergistic effects against vancomycin-sensitive Enterococcus species and MSSA were observed, too. Lastly, it was reasoned that α-mangostin might play a role in tackling infections with VRE and MRSA alongside antibiotics, however, this has yet to be validated by in vivo research [27].

In their study, Seesom et al. addressed the efficacy of crude extract and purified xanthones from G. mangostana as therapeutic agent against Leptospira species [28]. Both the four tested crude extracts and the five isolated mangosteen xanthones demonstrated anti-leptospiral potency, as findings from broth microdilution tests showed. Crude extracts of G. mangostana had MICs of 200 to ≥800 μg mL⁻¹ with respect to the human-pathogenic Leptospira interrogans (L. interrogans) serovars Bataviae, Autumnalis, Javanica, and Saigon. The MIC of the strongest tested compound, which was garcinone C, numbered 100 μg mL⁻¹ against L. interrogans, whereas a MIC of 200 μg mL⁻¹ was identified for the non-pathogenic Leptospira biflexa serovar Patoc. Nonetheless, established antibiotics demonstrated superiority over garcinone C in the treatment of Leptospira species, as their MIC values were lower. Of note, synergism was observed between γ-mangostin and penicillin G against the tested L. interrogans serovars Bataviae, Autumnalis, and Javanica with FIC indices of 0.52, 0.50, and 0.04, respectively. By contrast, antagonism within the combined treatment was observed in the use against L. interrogans serovar Saigon, as suggested by a FIC index of 4.03. Alone, γ-mangostin exhibited strong anti-leptospiral capacity with MICs usually within the range of 100–200 μg mL⁻¹; however, L. interrogans serovar Autumnalis necessitated a MIC higher than 800 μg mL⁻¹. By and large, the authors underscored the therapeutic potential of G. mangostana compounds in leptospirosis, stressing the promising application of γ-mangostin concomitantly with penicillin G [28].

Phitaktim et al. examined the combined use of α-mangostin derived from G. mangostana and the antibiotic oxacillin against oxacillin-resistant Staphylococcus saprophyticus (S. saprophyticus) [29]. Applied individually, the MIC against oxacillin-resistant S. saprophyticus were 8 and 128 μg mL⁻¹ of α-mangostin and oxacillin, respectively. Concentrations of only 2 μg mL⁻¹ α-mangostin together with 16 μg mL⁻¹ oxacillin caused a substantial decline of viability of the oxacillin-resistant S. saprophyticus strain DMST 27055 in a kill curve assay. Dose-dependency of the inhibition of β-lactamase by α-mangostin was found in enzyme assays. Cytotoxicity was observed in MTT assays at α-mangostin and oxacillin concentrations of 128 and 1,024 μg mL⁻¹, respectively. These numbers corresponded to 16 and 8 times the respective MIC for application against the S. saprophyticus strain. Transmission electron micrographs of the bacterial strain under exposure to the treatment combination demonstrated damage of peptidoglycans and cytoplasmic membranes. Damaged peptidoglycans were seen in confocal microscopic images as well, but also DNA leakage. Moreover, an amplified cytoplasmic membrane permeability of the S. saprophyticus strain was detected. According to the authors, the above described findings corroborated their hypothesis of synergism between α-mangostin and oxacillin with regard to anti-bacterial efficacy. Notwithstanding, it was conceded that the translatability of the phytopharmaceutical-synthetic antibiotic synergy to humans remains unclear, warranting clinical trials in the further research on this topic [29].

3.4 Potential aid to wound healing

For their study, Pooprommin et al. created wound dressings in the form of hydrogel films based on alginate and pectin, containing niosome-enclosed mangosteen extract [30]. Using an in vitro setting, improved anti-bacterial activity of the hydrogel film was assumed at a medium dose of 15 mg of mangosteen extract loaded niosomes. In particular, the mangosteen extract (concentrations ranging from 0.02 to 2.93 mg mL⁻¹) was employed against S. epidermidis and S. aureus. Its anti-bacterial efficacy was, among others, attributed to pseudolysin inhibitors like threo-isocitric acid and palmitic amide, both found in the mangosteen extract. The MIC₅₀ and MIC₉₀ values numbered 0.54 ± 0.01 and 1.27 ± 0.03 mg mL⁻¹ as well as 0.17 ± 0.01 and 0.61 ± 0.02 mg mL⁻¹ in case of S. aureus and S. epidermidis, respectively. However, no anti-bacterial activity (as assessed by the agar diffusion method) was observed at doses of mangosteen extract lower than 0.15 and 0.3 mg with respect to S. aureus and S. epidermidis. While the bacterial inhibition due to released mangosteen extracts declined over time, the concentration of free mangosteen extract rose. Hence, continued efficacy was assumed. Regarding fibroblasts and erythrocytes, no substantial cytotoxicity emerged. Moreover, albino rabbits to which patches containing mangosteen extract loaded niosomes were administered showed no skin irritation, i. e. they presented with neither an erythema nor an edema 72 h after treatment [30].

So-In and Sunthamala reported their findings from experiments with a G. mangostana extract in a rabbit model of S. aureus induced dermatitis [31]. An initial phytochemical analysis of G. mangostana crude extract confirmed the presence of the following compounds: alkaloids, phenolics, tannins, flavonoids, coumarin, terpenoids, and glycosides. Judging by skin appearance of the rabbits following the wound infection with S. aureus, treatment with G. mangostana had a positive influence on wound healing, i. e. no remaining lesions were found at day 4 of extract administration. Of note, the application of G. mangostana extract led to a substantial reduction in S. aureus, which was comparable to the anti-bacterial effect of the antibiotic bacitracin employed as a cream. Increased expression of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and interferon gamma was noticed in S. aureus infected rabbits not receiving any therapeutic substance in contrast to rabbits being given G. mangostana extract, which led to a reduction in inflammatory mediators. Similiarly, treatment with G. mangostana extract was associated with an attenuated concentration of thiobarbituric acid reactive molecules and level of lipid peroxidation; both were elevated in unimpeded pathogen presence. Compared to other tested herbs, which were Thunbergia laurifolia, C. longa, and Andrographis paniculata, G. mangostana turned out to be the most effective extract for therapeutic use in S. aureus induced dermatitis, entailing possible suitability as phytopharmaceutical topical medication [31].

Charernsriwilaiwat et al. tested the feasibility and anti-bacterial activity of nanofiber mats based on chitosan carrying extracts from G. mangostana [32]. The extracts with 1, 2, and 3 wt% α-mangostin were inserted into a polymer solution termed “CS-EDTA/PVA” and subsequently electrospun, producing nanofibers. Results of an in vitro release study suggested the fast release of α-mangostin from the nanofiber mats, with 80% being released within an hour. For a duration of three months, mats sustained 90% of α-mangostin. While concentrations between 7.5 and 10.0 mg mL⁻¹ of extracts led to a notable reduction in viability of normal human foreskin fibroblasts, no relevant cytotoxicity was detected in the concentration range of 1–5 mg mL⁻¹. The nanofiber mats equipped with G. mangostana extracts, that are 1, 2, and 3 wt% α-mangostin, induced bacterial inhibition of S. aureus and E. coli at MBC values of 2.0, 1.0, and 0.5 mg mL⁻¹, equaling the respective MIC values. Making use of Wistar rats, wound healing tests were carried out in vivo. In fact, mats-treated wounds healed faster than wounds provided only with gauze, suggesting relevant anti-bacterial effects in vivo. Therefore, electrospinning appeared to be compatible with the preservation of α-mangostin's anti-bacterial efficacy, thus, corroborating its utility as a dressing beneficial to the healing of infected wounds [32].

3.5 Staphylococcal skin infections

For their experiments, Tatiya-aphiradee et al. employed a superficial skin infection model in mice, addressing the antibacterial efficacy of pericarp extract from G. mangostana against MRSA in vivo [33]. Using ethanol and methanol, two extracts were prepared: GM-EtOH and GM-MeOH, respectively. Considering the share of α-mangostin in dry weight, GM-EtOH contained 13.20%, whereas GM-MeOH contained only 9.83%. At first, in vitro experiments were performed, revealing the superiority of GM-EtOH over GM-MeOH (each at 5 mg) in use against the strain MRSA DMST 20651 with inhibition zones measuring 13.17 ± 1.15 and 12.50 ± 0.00 mm, respectively. Interestingly, the administration of GM-EtOH and GM-MeOH against MSSA resulted in respective zones of inhibition with diameters of 12.75 ± 1.04 and 13.25 ± 0.65 mm. Even α-mangostin alone at 0.66 mg (being equivalent to the mass within 5 mg of GM-EtOH) led to inhibition zones of 11.17 ± 0.29 mm and 10.00 ± 0.00 mm when tested against MSSA and MRSA, respectively. In comparison, the antibiotics gentamicin (10 μg) and erythromycin (15 μg) had anti-bacterial effects against MSSA only, with no inhibition zone at all in case of MRSA. Furthermore, GM-EtOH showed MIC values of 14 μg mL⁻¹ and 17 μg mL⁻¹ against MSSA and MRSA; lower MIC values were dectected in both cases compared to GM-MeOH, validating the decision for GM-EtOH in the trials on mouse skin. In fact, even MBC values of 30 μg mL⁻¹ GM-EtOH and of 100 μg mL⁻¹ α-mangostin were determined against MRSA. Over the course of treatment, GM-EtOH was capable of a staphylococcal reduction in the wounds of mice to a similar level of the control group without such an initial infection. Also, the use of α-mangostin and erythromycin, each applied individually, resulted in a continuous reduction of MRSA growth, achieving the non-infection group's level at the third day of application. The administration of both GM-EtOH and erythromycin led to a complete healing of wounds on day 9, whereas following gentamicin application the wounds still presented with pus and prominent bacterial growth. However, the wounds treated with α-mangostin may have not healed fully on day 9, but at least they demonstrated clinical improvement with only little remaining pus. In a nutshell, those findings prompted the researchers to infer pronounced potential of GM-EtOH as therapeutic agent in staphylococcal skin infections [33].

Tatiya-aphiradee et al. reported their results of further experiments in another publication focusing on the anti-inflammatory effects of pericarp extract from G. mangostana, again in a superficial skin infection model in mice with MRSA as causative pathogen [34]. Following topical application of the pericarp ethanolic extract, a sustained reduction in MRSA colonies was noted, thus, full macroscopic recovery of the infected wounds was reached on the tenth day. However, wounds to which only α-mangostin was provided did not reach complete recovery and contained highest bacterial burdens. While no inflammatory cell infiltration was found in wounds following pericarp extract administration, mast cells and neutrophils infiltration persisted in wounds exposed to α-mangostin. For comparison, untreated wounds infected with MRSA came along with substantial levels of TNF-α, interleukin-6, and interleukin-1β. Hence, the diminished mRNA quantities of respective compounds were attributed to the pericarp extracts, being superior to α-mangostin for this purpose. Taking the overall experience into account, the suitability of ethanolic extracts from the pericarp of G. mangostana as a phytopharmaceutical candidate for therapeutic use in MRSA-induced skin infections was concluded, underscoring also favorable features like its anti-inflammatory potency [34].

3.6 Therapeutic option for acne

Phumlek et al. performed a study on a hydrogel patch based on mangosteen pericarp for therapeutic purposes in case of bacteria-induced acne [35]. The hydrogel patch consisted beyond the G. mangostana extract of carrageenan and locust bean gum powders. It exhibited anti-bacterial activities against Cutibacterium acnes (C. acnes), S. epidermidis, and S. aureus at a MBC/MIC ratio of 1–2, which was attributed to α-mangostin. Of note, the G. mangostana extract necessitated lower MIC and MBC values than the antibiotic clindamycin. About 30% of α-mangostin was released from the G. mangostana hydrogel patch within the first 30 min following application; and the release continued at an increasing rate until three hours after. No skin irritation was reported in the 30 healthy volunteers at 30 min and 24 h post patch removal, but at 11 days after patch removal two probands presented with allergic contact dermatitis following the application of a hydrogel patch containing 0.5% G. mangostana. Apart from the allergic reaction, the overall experience with the hydrogel patch comprising components of G. mangostana prompted the authors to demand a phase II clinical trial study, proposing its potential use as an anti-acne facial mask [35].

Pothitirat et al. briefly reported their findings of experiments with fruit rind extracts from G. mangostana as anti-bacterial therapy of acne [36]. To begin with, extracts were created with hexane, dichloromethane, ethanol, and water for use against C. acnes strain ATCC 6919 and S. epidermidis strain ATCC 14990. Making use of thin-layer chromatography, the presence of α-mangostin within all extracts except of the water extract was detected. Involving a MIC against both pathogens of 3.91 μg mL⁻¹ as well as MBC values of 3.91 and 15.63 μg mL⁻¹, respectively, the dichloromethane extract was considered superior. Of note, the dichloromethane extract also contained the highest amount of α-mangostin (46.21% w/w). In contrast, the water extract, including only 0.54% w/w of α-mangostin, exhibited the weakest potency against both bacterial species with a MIC of 500 μg mL⁻¹ and a MBC exceeding 500 μg mL⁻¹. Since the anti-bacterial activity of the mangosteen extract was stronger against C. acnes than S. epidermidis, it was assumed that extract polarity had a relevant influence on the therapeutic efficacy. With those results in mind, the authors suggested to conduct further studies on the suitability of dichloromethane extract from G. mangostana against acne-inducing bacteria in animal models, especially addressing safety aspects in vivo [36].

3.7 Application in dental medicine

Janardhanan et al. evaluated the anti-cariogenic potential of G. mangostana [37]. As basis for their in vitro experiments served a crude chloroform extract of mangosteen pericarp. Making use of the agar well diffusion method, zones of inhibition were ascertained. The strongest anti-bacterial effect of G. mangostana was seen in tests with Lactobacillus acidophilus (L. acidophilus) und Streptococcus sanguinis, both of which were inhibited in zones of 13.6 mm diameter. Inhibition zones measuring 11.3 and 10.6 mm were achieved against Streptococcus oralis (S. oralis) and S. mutans, respectively. However, the zone of inhibition in case of Streptococcus salivarius came to only 3 mm. In general, the mangosteen pericarp extract proved to be superior to 0.2% chlorhexidine in terms of the observed zone of inhibition. L. acidophilus and S. oralis required the lowest MIC and MBC values with 25 mg mL⁻¹ and 50 mg mL⁻¹ as well as 50 mg mL⁻¹ and 100 mg mL⁻¹, corresponding to a MBC/MIC ratio of 2. Thus, the MIC (25 mg mL⁻¹) of mangosteen pericarp extract for L. acidophilus roughly matched the MIC of chlorhexidine (20 mg mL⁻¹). Since no further analysis of the ingredients was performed in this study, the bioactive agents in mangosteen pericarp remain to be explored, which also holds true for the anti-bacterial potential against Gram-negative pathogens of the oral cavity [37].

Widyarman et al. performed in vitro experiments with mangosteen peel extracts targeting S. mutans and P. gingivalis as pathogens causing caries and periodontal diseases [38]. First of all, a qualitative phytochemical screening of the ethanolic mangosteen pericarp crude extract was conducted, revealing the following metabolites: saponins, tannins, alkaloids, phenolics, flavonoids, triterpenoids, and glycosides. Indeed, the mangosteen peel extract achieved the inhibition of the S. mutans ATCC-3198 strain and the P. gingivalis ATCC-3327 strain. However, this effect was greater in the case of S. mutans, which was explained with the fact that α-mangostin damages peptidoglycans being less present in P. gingivalis. Considering the inhibition of biofilm formation, the most potent concentration and time of incubation were 100% in 6 h and 100% in 24 h for S. mutans and P. gingivalis, respectively. This anti-biofilm effect occurred in a dose-dependent manner. Further studies investigating the anti-bacterial efficacy of mangosteen peel extracts on other oral pathogens were called for, although the extract was already deemed a therapeutic candiate for the prevention of caries and periodontal disease [38].

Juntavee et al. examined a gel called “Apacaries”, comprising both a polyphenol derived from mangosteen extracts and papain, with regard to its anti-bacterial potency in in vitro use against S. mutans as causative agent of caries [39]. Administered against the S. mutans strain ATCC25175, the MIC and MBC values of the pericarp extract alone amounted to 250 μg mL⁻¹ and 1,000 μg mL⁻¹, respectively. A time-kill kinetics curve demonstrated that 50% of the bacterial burden was eliminated within approximately 5 s (and a lag time of 25 s) following the application of 1 mg mL⁻¹ of mangosteen extract, with no bacterial residue found at 60 s. However, best results were noticed when Apacaries gel (at 1 mg mL⁻¹) was employed, which was based on a 1.0/1.5 ratio mixture of mangosteen extract and papain. This mixed gel was capable to result in an inhibition zone measuring 12.33 ± 0.29 mm, for instance. Each alone, 0.1% mangosteen extract and 59.94% papain created inhibition zones with diameters of 8.83 ± 0.29 mm and 7.83 ± 0.58 mm, respectively. All in all, the combination of mangosteen extracts and papain in one gel proved to entail therapeutic potential against S. mutans, thus, warranting randomized controlled trials elucidating the in vivo antibacterial capacity [39].

4.1 Main findings

4.1.1 Antibacterial capacity and disease-alleviating features of bioactive molecules derived from the mangosteen fruit

Compounds and extracts derived from the mangosteen fruit exhibited pronounced anti-bacterial activity against a wide variety of pathogens, including multi-drug resistant species including MRSA and VRE [17–39]; an overview is provided in Table 1. Particularly often, α-mangostin was investigated as a major anti-bacterial agent [17–19, 21, 26, 27, 29, 33–36, 38]. Nevertheless, mangosteen extracts as a whole commonly proved to be superior to the isolated use of α-mangostin [33, 34]. Not only bacterial growth inhibition, but also bacterial elimination was observed in some studies [17, 32, 33, 35–37, 39]. In fact, mangosteen compounds counteracted even bacterial biofilms [23, 38]. These effects were typically dose-dependent [20, 24, 30, 38]. Since neither the variation of temperature and humidity nor the exposure to UV light and oxidative agency resulted in diminished anti-bacterial efficacy, strong stability of α-mangostin can be assumed [18, 19]. However, degradation of α-mangostin was achieved through high levels of acidity, necessitating larger doses for the maintenance of the respective activity [19]. The observations from in vitro experiments were usually validated in vivo, as demonstrated by improved wound healing, for instance [30–34]. In addition to bacterial eradication, reduced inflammatory immune responses were found following the administration of mangosteen-derived extracts or bioactive molecules [31, 34]. While no or only little toxicity at therapeutic concentrations was reported [18, 20, 23, 25, 29, 30, 32], allergic contact dermatitis developed as an adverse effect when a hydrogel patch containing a mangosteen pericarp extract was applied [35]. All in all, extracts and compounds drived from the mangosteen fruit displayed a marked potential as therapeutic option for bacterial infections of the skin, intestines, and oral cavity [18, 23, 30–39] (Fig. 3).

Table 1.

Overview (non-exhaustive) of compounds from Garcinia mangostana and tested bacteria For further details see the results section. Only exemplary references are indicated

Compounds

Bacteria

α-mangostin [17] γ-mangostin [28] garmoxanthone [22] isogarcinol [22] garcinone C [28] garcinone E [22] dulxanthone A [22] mangostanin [23]

Staphylococcus spp. (S. aureus, S. epidermidis, S. saprophyticus) [23, 29] Methicillin-resistant Staphylococcus aureus [26] Streptococcus spp. (S. mutans, S. pyogenes, S. sanguinis, S. oralis) [23, 37] Escherichia coli, Clostridium perfringens [18, 24] Vancomycin-resistant Enterococcus species, Enterococcus faecalis [20, 21] Klebsiella pneumoniae, Listeria monocytogenes [20] Vibrio vulnificus, Leptospira interrogans [22, 28] Porphyromonas gingivalis, Cutibacterium acnes [23, 35]

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Extracts and compounds (primarily α-mangostin) from Garcinia mangostana exhibited anti-bacterial capacity not only in vitro, but also demonstrated high potential for therapeutic use in infectious diseases of the skin, intestines, and oral cavity

This figure was partly created with free medical images from Servier Medical Art (smart.servier.com), licensed under CC BY 4.0

Citation: European Journal of Microbiology and Immunology 2025; 10.1556/1886.2025.00006

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4.2 Limitations

Since only one author of this review was involved in the identification of suitable literature and data extraction, errors or inaccuracies may be possible, although great care was taken. Also, we used neither other search engines beyond PubMed nor its Medical Subject Headings, which could have expanded the literature base. The full texts of two possibly relevant publications were unavailable.

Approximately 60% of the included articles (i., 14 out of 23) were published within the last ten years, indicating a high degree of topicality. In addition, many different researchers contributed to the articles, which forestalls a concentration risk. The great variety of experimental settings in terms of respective bacteria and infectiological objectives suggested a versatile applicability of therapeutic compounds derived from the mangosteen fruit.

Whether or to what extend those results can be extrapolated to humans, depends on further studies. In fact, it is precisely the heterogeneity that entails a reduced comparability of the various findings. Given the little evidence from clinical trials, ambiguities and obscurities remain to be resolved.