TABLE 1.

Immunomodulatory effects and mechanisms of the extracts of Zingiber and Alpinia species.

Species	Subject	Study design/method	Preparation	Immunomodulatory activity	Modulation	Parameter/mediator affected	Reference
Zingiber officinale	Osteoarthritis patients	Clinical study	Essential oil	Cytokine release	Suppression	TNF-α, IL-1β	Mozaffari-khosravi et al. (2016)
	Autoimmune encephalomyelitis mice	In vivo	Ethanol extract	Cytokine release	Suppression	IL-33	Jafarzadeh et al. (2014a)
	Fibromyalgia mouse	In vivo	Dried powder	Proinflammatory Mediators	Suppression	TXB2, PGE2, IL-1β, and NO	Montserrat-de paz et al. (2018)
	Osteoarthritis rats	In vivo	Ethanol extract	Cytokine Release	Suppression	IL-1β	Aborehab et al. (2017)
	Human T lymphocytes	In vitro	Methanol extract	Inflammatory cytokines	Stimulation	IL-8, TNF-α, and IFN-γ	Schoenknecht et al. (2016)
	Pulmonary inflammation model mouse	In vivo	Aqueous extract	Th1 and Th2 cell activity	Suppression	Th1 and Th2 cell	Ahui et al. (2008)
				Cytokine release	Suppression	IgE
	Human lymphocytes	In vitro	Powder	Cytokine release	Suppression	IL-2 and IL-10	Wilasrusmee et al. (2002)
	Encephalomyelitis model mice	In vivo	Ethanol extract	Cytokine release	Suppression	IL-23 and IL-17	Jafarzadeh et al. (2015a)
	OVA-induced allergic rhinitis in mice	In vitro	Oral supplement	Cytokine release	Suppression	Th1 and Th2 cell	Kawamoto et al. (2016)
	LPS-activated BV2 microglia	In vitro	Ethanolic extract	Cytokine release	Suppression	IL-1β, IL-6, and TNF-α	Ho et al. (2013)
	Tumor mouse model	In vivo	Ginger polysaccharide (UGP1)	Cytokine release	Stimulation	TNF-α, IL-2, and IL-6	Qian et al. (2023)
	Tumor mouse model	In vivo	Ginger polysaccharide (UGP1)	Cytokine release	Suppression	TGF-β and bFGF	Qian et al. (2023)
	BALF of BALB/c mice model of ovalbumin-induced allergic asthma	In vivo	Ethanol extract and aqueous extract	Total and differential count of granulocytes	Suppression	Eosinophils and neutrophils	Harun and Mohamad (2022); Khan et al. (2015)
	BALF of BALB/c mice model of ovalbumin-induced allergic asthma	In vivo	Ethanol extract and aqueous extract	Cytokine release	Suppression	IL-4, IL-5, and IgE	Harun and Mohamad (2022); Khan et al. (2015)
	Community-acquired pneumonia (CAP) patients	Clinical study	Z. officinale capsule 300 mg	Serum inflammatory markers	Suppression	Procalcitonin and NLR	Reviono et al. (2023)
	Peritoneal adhesion model of male Wistar rats	In vivo	Ethanol extract	Cytokine release	Suppression	IL-6, TNF-α, TGF-β1, and IL-10	Yahyazadeh et al. (2023)
Zingiber zerumbet	Human	In vitro	Ethanol extract	CD18 expression	Suppression	CD18	Akhtar et al. (2019)
	Neutrophil cell
	Mice	In vivo	Ethanol extract	CD11b/CD18 expression	Suppression	CD11b/CD18	Ghazalee, et al. (2019)
Zingiber cassumunar	Mice macrophages	In vitro	Ethanol extract	Cytokine release	Stimulation	IL-10 and IL-l4	Mahfudh et al. (2020a)
	Mice macrophages	In vitro	Ethyl acetate fraction	ROS enhance	Stimulation	CD36	Nurkhasanah and Sofyan (2019)
	Mice macrophages	In vivo	Ethyl acetate fraction	Cytokine release	Stimulation	IL-10 and IL-l4	Nurkhasanah and Sofyan (2019)
	Mice macrophages	In vitro	Chloroform fraction	Phagocytic effects	Stimulation	Phagocytes	Ramadhan et al. (2020)
	Adult asthmatic patients	Clinical study	Z. cassumunar capsule	Bronchial hyperresponsiveness	Suppression	Fractional exhaled nitric oxide	Dulpinijthamma et al. (2023)
Alpinia galanga	HaCaT keratinocyte cell	In vitro	Ethanol extract	Inflammatory cytokines	Suppression	NF-κB signaling	Saelee et al. (2011)
					Stimulation	TNF-α
	LPS-stimulated RAW 264.7 cell	In vitro	Ethanol extract	Cytokines release	Suppression	IL-6 and TNF-α	George et al. (2021)
	Mice	In vivo	Flavonoid fraction	Lymphocyte formation	Stimulation	Lymphocyte	Jain et al. (2012)
	Mice	In vivo	Flavonoid fraction	T-cell proliferation	Stimulation	T-cell proliferation	Jain et al. (2012)
Alpinia conchigera	LPS-induced RAW 264.7 cells	In vitro	Isolate	NF-κB activation	Suppression	NF-κB	Lee et al. (2006)
	MCF-7 cell	In vitro	Isolate	Dysregulation of NF-κB pathway	Suppression	NF-κB	In et al. (2011)
Alpinia katsumadai	OVA-induced asthma mouse model	In vitro	Ethanol extract	Cytokine release	Suppression	Th2-type cell	Lee et al. (2010)
						IgE and IgG2a
	Mouse paw edema	In vivo	Powder	Cytokine release	Suppression	NO, TNF-α, IL-1β, and IL-6	Li et al. (2015)
	Mouse paw edema	In vivo	Powder	iNOS and COX-2 expressions	Suppression	iNOS and COX-2	Li et al. (2015)
	Mouse paw edema	In vivo	Powder	NF-κB activation	Suppression	NF-κB	Li et al. (2015)
	Mouse paw edema	In vivo	Powder	ERK1/2, p38, and JNK/SAPK level	Suppression	ERK1/2, p38, and JNK/SAPK	Li et al. (2015)
	Allergic airway inflammation induced by OVA in mice	In vitro	Isolate	Inflammatory cytokines	Suppression	Th2 cell and IgE	Wang et al. (2017)
Alpinia oxyphylla	Monosodium iodoacetate (MIA)-induced rat model	In vitro	Ethanol extract	Cytokine release	Suppression	IL-1β, IL-6, and TNF-α	Lee et al. (2019)
	LPS-treated RAW 264.7 cell	In vitro	Ethanol extract	Cytokine release	Stimulation	ERK, JNK, and MAPK	Lee et al. (2019)
	Lipopolysaccharide-induced mice model of Alzheimer’s disease	In vivo	Petroleum ether extract of A. oxyphylla fructus	Cytokine release	Suppression	IL-1β	Guo et al. (2022); Wang et al. (2018)
Alpinia zerumbet	LPS-induced HAEC	In vitro	Essential oils	Inflammatory cytokines	Suppression	TLR4/NF-κB	Xiao et al. (2020)
	Endothelial cell	In vitro	Essential oil	Inflammatory cytokines	Suppression	NF-κB	Huang et al. (2017)
	Endothelial cell	In vitro	Essential oil	Inflammatory cytokines	Suppression	TNF-α and IL-8	Huang et al. (2017)
Alpinia officinarum	Macrophage cell and human peripheral blood mononuclear cells (PBMCs)	In vitro	Isolate	Cytokine release	Suppression	IL-1β	Yadav et al. (2003)
	Macrophage cell and human peripheral blood mononuclear cells (PBMCs)	In vitro	Isolate	Cytokine release	Suppression	TNF-α	Yadav et al. (2003)