Table 2. The preventive and therapeutic effects of mangosteen in various diseases.

Function		Study Design	Subject	Outcome	Conclusion	Ref.
Antioxidant property		In vitro	GMR, hexane,ethyl acetate, butanol,water fraction	The SOD level in GMR water fraction and TAS level in GMR ethyl acetate fraction were the highest	High DPPH capture activity	Tjahjani et al. (2014)
		In vivo	GMR	Reduce the redox imbalance and toxicity of liver tissue caused by long-term γ -ray irradiation, and improve the liver function, MDA content, antioxidant enzyme activity and NO level of damaged liver	Protective effect from irradiation-induced injury	Hassan et al. (2021)
		In vitro	MPW	Reduce lipid peroxidation and eliminated DPPH free radical,and inhibit the activities of β-secretase and acetylcholinesterase	Antioxidant and neuroprotective effects	Oh et al. (2021)
		In vivo	MCD	Increase the activities of glutathione peroxidase and catalase, reduce the oxidative stress in muscles, and increase the clearance rate of lactic acid	Reduce muscle fatigue after exercise	Chang et al. (2020)
Anti-inflammatory properties		In vivo	GME	Decrease mRNA level, restored the expression of these genes to normal level and down-regulated the expression of pro-inflammatory cytokines	Antibacterial, anti-inflammatory, and wound healing effects	Tatiya-aphiradee, Chatuphonprasert & Jarukamjorn (2019)
		In vivo	GMR	Reduce inflammatory markers (TNF- α, IL-6 and CRP) and down-regulate transcription factors NF- κB/TGF-B1 in liver tissue after long-term γ-ray irradiation	Protective effect from irradiation-induced injury	Hassan et al. (2021)
		In clinical	MAEC	Reduce crevicular IL-6, increase the salivary MMP-9, and reduce gingival inflammation	A potential to reduce gingival inflammation in the patients with gingivitis and incipient periodontitis	Park et al. (2021)
Antitumor property	Anti-breast tumor	In vivo	α-MG	Trigger PARP cleavage and induce apoptosis through PI3K/AKT signaling pathway targeting RXR α, and inhibits the migration and invasion of breast cancer cells	Inhibition effects of invasion and metastasis of MDA-MB-231 cells	Zhu et al. (2021)
			α-MG	Reduce the production of cancerous compounds	Inhibit the proliferation and apoptosis of multiple breast cancer cells	Herdiana et al. (2021)
		In vitro	α-MG	Inhibit the expression and intracellular activity of FAS, decrease the intracellular fatty acid accumulation, reduce cell viability, induce apoptosis of human breast cancer cells, increase the level of PARP cleavage products, and weaken the balance between anti-apoptosis and pro-apoptosis proteins of Bcl-2 family	Induce breast cancer cell apoptosis by inhibiting FAS	Li, Tian & Ma (2014)
	Anti-digestive tumor	In vitro+in vivo	α-MG	Reduce tumor size	Enhance the inhibition of sorafenib on the cell proliferation in HCC cell line	Wang et al. (2021)
		In vitro	Carnation flavone E	Induce a significant cell cycle stagnation in G0/G1 phase, induce apoptosis and necrosis in colorectal adenocarcinoma and human hepatocellular carcinoma cells	Anti-proliferation/cytotoxicity, induce cell killing effect	Mohamed et al. (2017)
			Mangosteen IV	Induce necrosis and apoptosis in HCT116 cells	Cytotoxic property
			α-MG	Induce apoptosis and necrosis of HepG2 cells, and moderate necrosis of HCT116 cells
		In clinical+ In vivo + In vitro	γ-MG	Inhibite GSK3 β-related signal pathway, and increase the level of miR-26b-5p	Overcome the 5- fluorouracil resistance induced by CAFs and the production of CSCs	Wu et al. (2022)
Diabetes prevention and treatment		In vivo	γ-MG	Inhibit α-amylase/ α-glucosidase through insulin sensitization, promote glucose intake and reduce sugar digestion	Anti-hyperglycemia activity	Chen et al. (2021)
		In vivo	Xanthones	Garcinone E was found to be the most effective PTP1B inhibitor	PTP1B-inhibitory activity	Hu et al. (2021)
		In clinical	Mangosteen extract	Improve the insulin sensitivity	Have a possible supplementary role in the treatment of obesity, insulin resistance, and inflammation	Watanabe et al. (2018)
Neurological system therapy	AD	In vivo	MX-IV	Reduce the oxidative stress, neuroinflammation and apoptosis via decrease the brain contents of MDA, H2O2, TNF- α and IL-6 and increase the GSH, and through the regulation of PI3K/Akt/GSK-3 β pathway, decrease the content of NADPH oxidase and the activity of cleaved caspase-3, decrease the number of amyloid plaques and the expression of phosphorylated tau, enhance the neuron survival and cognitive ability	Neuroprotective effects	Abdallah et al. (2021)
		In vitro	α-MG	Inhibite the cell death induced by oxidative stress in neurons by reducing BAX protein, caspase-3/7 activation and increasing anti-apoptotic BCL-2 protein, bind to the active site of SIRT1, and activate SIRT1/3-FOXO3a pathway	Potentially use as a promising anti-oxidative stress therapeutic compound to treat AD.	Ramage et al. (2004)
	PD	In vitro+in vivo	TA	Reduce apoptotic cell death in primary cortical neurons, attenuate the behavioral dysfunctions and dopaminergic neuron loss	Cytoprotective effect to dopaminergic neurons	Huang et al. (2020)
		In vitro	α-MG	Inhibite NF-kB and NADPH oxidase	Protactive effect to neurotoxicity.	Hu et al. (2016)
	Depression	In vivo	GME	Reverse hippocampal lipid peroxidation	Antidepressant-like effects.	Oberholzer et al. (2018)
Antiparasitic properties	Antimalarial properties	In vivo	γ-MG	InteractE with QR-2 includes hydrogen bond and aromatic-aromatic interaction	Inhibit QR-2	Liang et al. (2020)
		In vitro	GME	IC50 range from 0.41 to >100 μg/mL	Antimalarial activity and synergistic antimalarial activity with artemisinin	Tjahjani (2017)
		In vitro	α-MG	Have more active against the resistant Plasmodium FCR3 strain than δ-mangostin	Antimalarial effect	Upegui et al. (2015)
	Anti-Acanthamoeba properties	In vitro	Mangosteen extract and α-MG	Inhibite the growth of Amoeba	Anti-Acanthamoeba activity	Sangkanu et al. (2021)
		In vitro	Extract and pure compounds from mangosteen	Remove A. triangularis trophozoites within 24 h	Anti-Acanthamoeba activity	Sangkanu et al. (2022)
Other functions		In vivo	α-MG	Alleviate behavioral alterations, increase the levels of all inflammatory markers, Bax, and caspase-3	Therapeutic effect on neuropathic pain caused by chronic compression injury	Ghasemzadeh Rahbardar, Razavi & Hosseinzadeh (2020)
		In vivo	α-MG	Ameliorate doxorubicin cardiotoxicity in human chemotherapy without reduction in its anticancer effect	Protective effects on doxorubicin-induced cardiotoxicity	Eisvand et al. (2022)
		In vitro+in vivo	α-MG	Inhibit the formation of osteoclasts	May be a potential choice for the treatment of osteoclast-related diseases	Zhang et al. (2022)

Notes.

AD

Alzheimer’s disease

CAFs

Cancer-related fibroblasts

CRP

C-reactive protein

CSCs

Cancer stem cell-like cells

DPPH

1,1-diphenyl-2-picrylhydrazyl

FAS

Fatty acid synthase

FCR3

Falciparum chloroquine-resistant

FOXO3a

Forkhead box protein O3a

GME

Garcinia mangostana Linn. Pericarp extract

GMR

Garcinia mangostana L rind

GSH

Glutathione

GSK3 β

Glycogen synthase kinase 3 β

HCC

Hepatocellular carcinoma

H₂O₂

Hydrogen peroxide

IC50

Inhibitory concentration

IL-6

Interleukin-6

MAEC

Mangosteen and propolis extracts

MCD

Mangosteen concentrate drink

MDA

Malonaldehyde

MMP-9

Matrix metalloproteinase-9

MPW

Mangosteen peel powder

MX-IV

Mangostanone IV

NADPH

Nicotinamide adenine dinucleotide phosphate

NF- κB

Nuclear factor κ-B

NO

Nitric oxide

PARP

Poly ADP-ribose polymerase

PD

Parkinson’s disease

PI3K

Phosphatidylinositol 3 kinase

PKB

Protein kinase B

PTP1B

Protein tyrosine phosphatase 1B

QR-2

Quinone reductase 2

RXR α

Retinoid × receptor α

SIRT1

Sirtuin 1

SOD

Suberoxide dismutase

TA

Tovophyllin A

TAS

Total antioxidant

TGF-B1

Transforming growth factor-B1

TNF- α

Tumor necrosis factor- α