Table 2.

Mechanism of action of extracts and isolates of Lamiaceae species with anti-allergic activity.

Plant name	Plant part used	Isolated compound/ extract used	Chemical class	Assay type	Mechanism of action/conclusion	References
Clerodendron phlomidis Linn.	Leaves	Aqueous extract	–	In vivo	Concentration of 100 mg/kg potently reduced blood eosinophil count, mast cell degranulation and histamine release in sensitized mice.	(Vadnere et al., 2007)
				Ex vivo	Potent antagonizing effect of histamine-induced goat tracheal contraction at doses of 4 mg/ml and 10 mg/ml.	(Vadnere et al., 2007)
Clerodendrum serratum (Linn.) Moon	Root and stem	Aqueous extract	–	In vivo	Root extract resulted in no significant increase of leucocyte and eosinophil count at 260 mg/kg in milk-induced leucocytosis mice and prolonged PCD at 156 mg/kg in egg albumin-sensitized guinea pigs.	(Bhangare et al., 2012)
Clerodendron trichotomum Thunb.	Leaves	Acteoside (22)	Phenylpropanoid glycoside	In vivo	At dose of 50 mg/kg significantly inhibited eosinophil infiltration, decreased histamine content and phospholipase A2 activity in BALF while at 25 mg/kg, recruitment of leukocytes was suppressed and inhibited sRaw in both IAR and LAR in sensitized guinea pigs model.	(Lee et al., 2011b)
Clinopodium gracile (Benth.) Matsum var. multicaule	Whole plant	Aqueous extract	–	In vivo	Compound 48/80-induced mice were observed with concentration-dependently reduced anaphylactic death with intraperitoneally administration at concentrations ranging from 1-100 mg/kg and the same reduction manner was seen in IgE-mediated PCA reaction.	(Park et al., 2010)
				In vitro	Dose-dependent inhibition of histamine release inhibition from RPMC and HMC-1 cells respectively across 1-100 µg/ml. Allergic inflammation reduced with the attenuation of intracellular calcium, NF-κB, gene expression and secretion of TNF-α and IL-6 stimulated by PMACI in HMC-1 cells.	(Park et al., 2010)
Dracocephalum argunense Fisch.	Whole plant	Aqueous extract	–	In vivo	Significant inhibition of systemic anaphylaxis with intraperitoneal administration of aqueous extract in mice at concentration range of 0.01–1 g/kg. Serum histamine and PCA inhibition were reduced in a dose-dependent manner.	(Kim et al., 2006; Kim and Shin, 2006)
				In vitro	Decreased intracellular calcium and histamine release from RPMC in dose dependent manner with concentrations of 0.001–1 mg/ml. TNF-α and IL-6 gene expression in HMC-1 cells were inhibited across doses ranging from 0.01–1 mg/ml with the involvement of NF-κB attenuation.	(Kim et al., 2006; Kim and Shin, 2006)
Elsholtzia ciliate (Thunb.) Hyland	Whole plant	Aqueous extract	–	In vivo	Serum histamine, systemic anaphylaxis and PCA reaction observed with dose-related inhibition at concentrations of 10–1,000 mg/kg.	(Kim et al., 2011)
				In vitro	Significantly inhibited histamine release at 10 and 100 µg/ml of aqueous extract and recorded with reduction of PMACI-stimulated intracellular calcium at 100 µg/ml of aqueous extract pretreatment in HMC-1 cells. Gene expression and production of IL-6, IL-1β and TNF-α were suppressed through inhibition of NF-κB activation and p38 MAPK pathway with concentrations ranging from 1-100 µg/ml.	(Kim et al., 2011)
Isodon japonicas Hara	Whole plant	Aqueous extract	–	In vivo	Challenged-mice protected from systemic allergic death and PCA with intraperitoneal administration of extract at concentration of 0.1 g/kg.	(Kim et al., 2004; Shin et al., 2004)
				In vitro	Dose-dependently decreased histamine release from RPMC stimulated by compound 48/80 or anti-DNP IgE at doses ranging from 0.001-1 mg/ml and reduced gene expression and production of TNF-α and IL-6 in PMACI-stimulated HMC-1 cells.	(Kim et al., 2004; Shin et al., 2004)
Lagochilus leiacanthus Fisch. & C.A.Mey.	Whole plant	5,2’,6’-trihydroxy-7,8-dimethoxyflavanone (23), 5,2’,6’-trihydroxy-6,7,8-trimethoxyflavanone (24), 5,2’-dihydroxy-6,7,8,6’-tetramethoxyflavanone (25), Oroxylin-A (14), Hispidulin (26), 5,2’,6’-trihydroxy- 6,7,8-trimethoxyflavone (27), 5,7,2’-trihydroxy-8,6’- dimethoxyflavone (28), 5,6,2’-trihydroxy-7,8,6’-trimethoxyflavone (29)	Flavonoid	In vitro	Significantly inhibited the release of β-hexosaminidase from RBL-2H3 cells with IC50 values ranging from 13.5-48.9 µM.	(Furukawa et al., 2011)
Lycopus lucidus Turcz.	Aerial part	Rosmarinic acid (1), clinopodic acid C (17), lycopic acid A (19), clinopodic acid E (18), lycopic acid B (20), scizotenuin A (21)	Phenylpropanoid	In vitro	Acted as hyaluronidase inhibitor with IC50 of 309, 80.1, 134, 82.8, 141 and 241 µM respectively.	(Murata et al., 2010)
	Whole plant	Aqueous extract	–	In vivo	Systemic anaphylactic death and PCA reaction reduced dose-dependently across concentrations of 0.005–0.1 g/kg in sensitized mice.	(Shin et al., 2005)
				In vitro	Histamine release potently reduced in compound 48/80 or anti-DNP IgE-stimulated RPMC corresponded to decreased intracellular calcium at dose range of 0.01–1 mg/ml. Attenuation of NF-κB caused a reduction in downstream cytokines, such as TNF-α and IL-6 expression.	(Shin et al., 2005)
Marrubium vulgare Linn.	Aerial part	Marrubiin (30)	Furane labdane diterpene	In vitro	Maximal inhibition (67.6 ± 4%) of OVA-induced allergic oedema was achieved at dose of 100 mg/kg in actively sensitized mice.	(Stulzer et al., 2006)
Melissa officinalis Linn.	Leaves	Rosmarinic acid (1)	Phenylpropanoid	In vitro	Exhibited potent suppressive effect on hyaluronidase with 1.0 ± 0.3% of enzyme activity.	(Ippoushi et al., 2000)
Mentha arvensis Linn.	Leaves, roots and stem	Ethanolic and aqueous extract	–	In vivo	100 µg/ml ethanolic leaf and root extract showed potent histamine inhibition at 57% and 53% respectively in mice.	(Malik et al., 2003)
	Whole plant	Aqueous extract	–	In vivo	Anal administration of 0.05 g/kg extract protected mice from anaphylactic death. PCA reaction reduced dose-dependently with intraperitoneal, oral and intravenous administration of extract.	(Shin, 2003)
				In vitro	Significant reduction in histamine release at 0.1 and 1 mg/ml of extract in compound 48/80-induced and anti-DNP IgE-mediated model in RPMC. TNF-α production reduced significantly at concentration of 0.1 mg/ml in RPMC.	(Shin, 2003)
	–	Essential oil	–	In vivo	Dose-dependently reduced histamine-induced bronchoconstriction in guinea pigs at 200 and 400 µl/kg and significantly reduced eosinophil count, serum IgE level and BALF eosinophils in OVA-sensitized mice at 200 µl/kg.	(Sharma et al., 2018)
Mentha haplocalyx Briq.	Aerial part	Ethanolic extract	–	In vivo	Observed with inhibition of eosinophil infiltration, TH2 cytokines (IL-4, IL-5) expression and production in OVA-sensitized mice.	(Lee et al., 2011a)
Mentha piperita Linn.	Leaves	50% ethanolic eluate	–	In vivo	Decreased nasal responses in antigen-induced rats at 300 and 1,000 mg/kg.	(Inoue et al., 2001)
				In vitro	Recorded with potent inhibition of histamine release from RPMC with IC50 of 2.55 (1.42–3.94) µg/ml.	(Inoue et al., 2001)
	Leaves	Luteolin-7-O-rutinoside (31)	Flavonoid glycoside	In vivo	Reduced frequency of sneezing at 100 and 300 mg/kg while nasal rubbing was seen in antigen-induced rats at 100 mg/kg or more.	(Inoue et al., 2002)
				In vitro	Suppression of histamine release from compound 48/80-induced RPMC with IC50 value of 21.9 µM.	(Inoue et al., 2002)
Mentha piperita var. citrata (Ehrh.) Briq.	Leaves	5,6,4’-trihydroxy-7,8-dimethoxyflavone (32), 5,6,4’-trihydroxy-7,8,3’- trimethoxyflavone (33), 5,6-dihydroxy-7,3’,4’- trimethoxyflavone (34), 5,6-dihydroxy-7,8, 3’, 4’- tetramethoxyflavone (35), 5,6-dihydroxy-7,8, 4’-trimethoxyflavone (36)	Flavonoid	In vitro	Significantly reduction of β-hexosaminidase release from RBL-2H3 at IC50 range of 2.4–6.7 µM.	(Sato and Tamura, 2015)
Mentha spicata L. var. crispa Benth.	Leaves	5,6-dihydroxy-7,8,3’,4’-tetramethoxyflavone (35), 5,6,4’-trihydroxy-7,8,3’-trimethoxyflavone (33), (3R)-1-octan-3-yl β-D-glucopyranoside (37)	Flavonoid and aliphatic glycoside	In vivo	Demonstrated β-hexosaminidase release suppression from rat basophils at 56, 6.4 and 560 µM respectively.	(Yamamura et al., 1998)
Minthostachys verticillata (Griseb.) Epling	Leaves and stems	Essential oil	–	In vitro	β-hexosaminidase release from human basophils was diminished by 32.15% to 39.72% as comparable to dexamethasone and theophylline.	(Cariddi et al., 2007)
	Leaves and stems	Limonene (38), Pulegone (39), Menthone (40)	Monoterpene	In vivo	(38) maximally suppressed PCA reaction in challenged-mice at 250 mg/kg.	(Cariddi et al., 2011)
				In vitro	The combination of the three constituents in essential oil significantly suppressed the production of IL-13 from human PBMC. Potent inhibitory effect on β-hexosaminidase release from human basophils was observed with a concentration range of 10–40 µg/ml.	(Cariddi et al., 2011)
Mosla chinensis Max.	Whole plant	Aqueous extract	–	In vivo	Observed with concentration dependent suppression of systemic anaphylaxis and PCA reaction with doses of ranging from 10–1,000 mg/kg in sensitized mice.	(Kim et al., 2012)
				In vitro	Decreased intracellular calcium caused a dose-dependent reduction of histamine release from RPMC and reduced NF-κB activation resulted in decreased downstream TNF-α, IL-6, IL-8 expression in PMACI-stimulated HMC-1 cells.	(Kim et al., 2012)
Mosla dianthera Maxim.	Whole plant	Aqueous extract	–	In vivo	Challenged-mice recorded with zero mortality due to systemic shock with pretreatment of 1,000 mg/kg and reduced PCA reaction in a dose-dependent manner across the range of 1–1,000 mg/kg.	(Lee et al., 2006)
				In vitro	Attenuation of histamine release from RPMC at doses ranging from 0.001–1 mg/ml and decreased intracellular calcium, NF-κB activation, gene expression and secretion of TNF-α, IL-6, IL-8 in PMACI-stimulated HMC-1 cells.	(Lee et al., 2006)
Nepeta bracteata Benth.	Whole plant	Crude aqueous extract	–	In vivo	Medium dose (not specified dose) exhibited the most potent reduction in the number of TH17 cells, increased number of Treg cells in OVA-sensitized mice and decreased eosinophil infiltration in BALF.	(Wang et al., 2016)
Ocimum basilicum Linn.	Leaves	Acetone and hydro-methanol extract	–	In vitro	Achieved histamine release suppressive effect of 35.35% and 50.76% respectively at 100 µg/ml.	(Kaur et al., 2018)
Ocimum gratissimum Linn.	Leaves	Methanolic extract	–	In vivo	Significantly suppressed number of eosinophils, decreased IL-4 level, reduced level of eosinophil peroxidase in BALF and lungs and decreased airway mucus hypersecretion at 100 mg/kg.	(Costa et al., 2012)
Ocimum sanctum Linn.	Leaves and seeds	Dried and fresh leaves ethanolic extract, volatile oil from fresh leaves and fixed oil from seeds	–	In vivo	Guinea pigs were protected from both histamine-induced and acetylcholine-induced preconvulsive dyspnoea with pretreatment of fresh leaves ethanolic extract, volatile oil and fixed oil.	(Singh and Agrawal, 1991)
	Leaves	Ethanolic extract	–	In vivo	Exhibited significant mast cell stabilizing potential, inhibition of IgE and delayed onset of histamine-induced bronchospasm with 64.25 ± 9.51%, 25.80 ± 4.85 ng/ml and 440 s respectively.	(Sridevi et al., 2009)
	Leaves	Ethanolic extract and isolated flavonoidal fraction	–	In vivo	Sensitized rats showed with significant mast cell stabilization of 67.24 ± 2.94% with extract administration and 60.48 ± 2.72% with fraction administration.	(Choudhary, 2010)
Perilla frutescens Britton	Whole plant	Aqueous extract	–	In vivo	Exhibited dose-dependent inhibition of compound 48/80-induced plasma histamine release at concentration range of 0.01–1 g/kg in sensitized rats. Marked suppression of PCA reaction at doses of 0.1 and 1 g/kg.	(Shin et al., 2000)
				In vitro	At concentration range of 0.001–1 mg/ml, histamine release and TNF-α production were decreased dose-dependently in stimulated RPMC. cAMP level in RPMC significantly increased at 1 mg/ml.	(Shin et al., 2000)
	Whole plant	Rosmarinic acid (1), Apigenin 7-O-[β-glucuronosyl(2→1) β-glucuronide] (2)	Flavonoid and flavonoid glycoside	In vivo	(1) and (2) suppressed PCA reaction in sensitized mice with percentage inhibition of 41% and 32% respectively.	(Makino et al., 2001)
	Leaves	Luteolin (3)	Flavonoid	In vivo	Sensitized mice showed with decreased oxazolone-induced ear odema with oral administration of 1 mg of (3). Dose-dependent inhibition of TNF-α production occurred at dose range of 1–1,000 µg.	(Ueda et al., 2002)
	Leaves	Rosmarinic acid (1)	Phenylpropanoid	In vivo	Equivalent PCA reaction suppression was achieved by 19 mg/kg of (1) as compared to 150 mg/kg of tranilast, the positive control.	(Makino et al., 2003)
	Leaves	Rosmarinic acid (1)	Phenylpropanoid	In vivo	Oral administration of (1) by Der f-sensitized mice caused reduction in allergen-specific immunoglobulin, eosinophil infiltration, eosinophil counts in BALF, eotaxin, IL-4 and IL-5 expression at concentration of 1.5 mg/day.	(Sanbongi et al., 2004)
	Leaves	Ethanol extract	–	In vivo	TH2 cytokines (IL-5 and IL-13), serum IgE level, eosinophil infiltration, histamine and eotaxin in BALF were suppressed in OVA-sensitized BALB/c mice.	(Chen et al., 2015)
	Leaves	Luteolin (3)	Flavonoid	In vivo	Compound 48/80- or serotonin-induced scratching behaviour and vascular permeability were reduced dose-dependently at 5, 10 and 20 mg/kg in sensitized mice.	(Jeon et al., 2014)
				In vitro	Dose-dependent reduction of compound 48/80-induced histamine release from RPMC marked at 5, 10 and 20 µM. Diminished production of TNF-α (31.9%-76.8%) and IL-1β (27.3%-81.2%) in PMACI-stimulated HMC-1 cells at a range of 5–20 µM of (8).	(Jeon et al., 2014)
	Leaves	Aqueous fraction	–	In vivo	DNFB-sensitized mice experienced 35% reduction of ear swelling symptom at dose of 100 µg/ml.	(Heo et al., 2011)
				In vitro	At 100 µg/ml, eosinophil counts reduced by 73.7% accompanied with decreased expression of MMP-9 and IL-31 in mice ear tissues. T-bet protein expression was augmented and resulted in TH1/TH2 balance.	(Heo et al., 2011)
	Leaves	Methanolic extract	–	In vitro	Dose-dependent reduction of IL-4, IL-5, IL-13 and GM-CSF production in DP2-stimulated BEAS-2B cells at concentration range of 5-50 µg/ml with involvement of decreased phosphorylation of JNK and p38.	(Liu et al., 2013)
	Leaves	Rosmarinic acid methyl ester (41)	Phenolic compound	In vitro	Possessed potent inhibitory activity on β-hexosaminidase from RBL-2H3 cells with IC50 of 9.9 ± 0.8 µg/ml.	(Zhu et al., 2014)
	Leaves	8-hydroxy-5,7-dimethoxyflavanone (4)	Flavanone	In vivo	Oral administration of (4) inhibited PCA reaction at dose of 5 mg and allergic nasal response at dose of 1.5 mg.	(Kamei et al., 2017)
				In vitro	Significant suppressive effect on histamine release from RBL-2H3 cells was observed with IC50 of 68.5 µM.	(Kamei et al., 2017)
	Leaves	Crude extract	–	In vivo	Decreased serum IgE level was observed in the blood of Der f-challenged mice.	(Komatsu et al., 2016)
				In vitro	Reduced CD4+/CD8+ ratio in splenic T lymphocytes with percentage of 1.50 ± 0.07%.	(Komatsu et al., 2016)
Phlomis umbrosa Turcz.	Roots	Aqueous extract	–	In vivo	At dose of 1 g/kg, plasma histamine release only recorded with 0.023 ± 0.002 µg/ml in compound 48/80- sensitized mice. Anal, oral and intraperitoneal administration of 0.01–1 g/kg extract resulted in dose-dependent reduction in PCA reaction.	(Shin et al., 2008; Shin and Lee, 2003)
				In vitro	Significant inhibition of histamine release from RPMC activated by compound 48/80 or anti-DNP IgE recorded at doses of 0.1 mg/ml and 1 mg/ml. Extract attenuated the secretion of IL-1β, IL-6 and TNF-α in PMACI-stimulated HMC-1 cells.	(Shin et al., 2008; Shin and Lee, 2003)
Pogostemon cablin (Blanco) Benth	–	Aqueous extract	–	In vivo	Intraperitoneal administration of extract caused a dose-related suppression of systemic anaphylaxis induced by compound 48/80 in sensitized mice across doses of 10–1,000 mg/kg. At doses ranging from 1–1,000 mg/kg, PCA reaction induced by DNP-HSA was reduced in a concentration-dependent manner in sensitized rats.	(Yoon et al., 2016)
				In vitro	Suppressed the release of histamine and β-hexosaminidase from RPMC across concentrations of 1–1,000 µg/ml. Expression and secretion of TNF-α, IL-6 and IL-8 was inhibited in HMC-1 cells at doses of 1–100 µg/ml due to the attenuation of NF-κB activation.	(Yoon et al., 2016)
	–	Patchouli oil	–	In vivo	Significant reduced PCA reaction in ovalbumin-challenged rats and suppressed delayed-type hypersensitivity at doses of 20, 40 and 80 mg/kg of Patchouli oil.	(He et al., 2013)
				Ex vivo	Decreased contraction responses in guinea pig ileum at concentrations of 0.01, 0.02 and 0.04 mg/ml of Patchouli oil.	(He et al., 2013)
Prunella vulgaris var. lilacina Nakai	Whole plant	2α,3α-dihydroxyurs-12-en-28-oic acid (42)	Triterpenoid	In vitro	Significant suppressive effect on β-hexosaminidase from RBL-2H3 with IC50 value of 57 µM.	(Ryu et al., 2000)
	Whole plant	Aqueous extract	–	In vivo	At doses of 0.5 and 1 g/kg, sensitized rats completely protected from anaphylatic death. Oral administration of extract with doses ranging from 0.001–1 g/kg dose-dependently reduced PCA reaction.	(Kim et al., 2007; Shin et al., 2001)
				In vitro	Inhibition of intracellular calcium level caused downstream decreased release of histamine from RPMC in a concentration dependent manner with concentration range of 0.001–1 mg/ml. RPMC also showed with significant reduction of TNF-α production with the pretreatment of 0.01 mg/ml and 0.1 mg/ml.	(Kim et al., 2007; Shin et al., 2001)
	Spike	β-amyrin (43), 2α,3α,23-trihydroxyursa-12,20(30)-dien-28-oic acid (44), Euscaphic acid (45)	Triterpenoid	In vitro	Observed with inhibition of histamine release from HMC-1 cells with 46.7%, 57.9% and 54.2% respectively.	(Choia et al., 2016)
Rosmarinus officinalis Linn.	Leaves	Carnosic acid (5)	Polyphenol	In vivo	PCA reaction was significantly suppressed at 100 mg/kg in sensitized mice with percentage inhibition of 67.1%.	(Mizushina et al., 2014)
				In vitro	(5) inhibited β-hexosaminidase release from PMACI A23187-stimulated RBL-2H3 cells at 10 µM.	(Mizushina et al., 2014)
Salvia miltiorrhiza Bunge	Roots	15,16-dihydrotanshinone-I (7), Cryptotanshinone (9)	Diterpene	In vitro	(7) and (9) significantly suppressed the release of β-hexosaminidase from RBL-2H3 cells with IC50 values of 16 ± 2.4 µM and 36 ± 3.7 µM respectively.	(Choi and Kim, 2004; Ryu et al., 1999)
	Leaves	Ethanolic extract	–	In vivo	Oral administration of 25–100 mg/kg extract dose-dependently inhibited PCA reaction in anti-DNP IgE-stimulated rats.	(Yang et al., 2008)
				In vitro	Dose-related inhibition of COX-1 and COX-2-dependent prostaglandin D2 production observed with IC50 values of 3.96 and 21.54 µg/ml respectively in BMMC. Suppression of leukotriene C4 generation and β-hexosaminidase release was seen in BMMC with IC value of 2.6 and 22.4 µg/ml.	(Yang et al., 2008)
	Rhizome	Tanshinone I (6), 15,16-dihydrotanshinone-I (7), Tanshinone IIA (8), Cryptotanshinone (9)	Diterpene	In vivo	(6), (7), (8) and (9) significantly suppressed PCA reaction at dose of 50 mg/kg with percentage inhibition of 59%, 49%, 35% and 32% respectively in sensitized mice.	(Trinh et al., 2010a)
				In vitro	Potent inhibition of IL-4 and TNF-α expression by (6), (7) and (8) at dose of 50 µM in RBL-2H3 cells.	(Trinh et al., 2010a)
	Roots	15,16-dihydrotanshinone-I (7)	Diterpene	In vitro	(7) at 20 µM produced 90% suppression on degranulation and generation of prostaglandin D2 and leukotriene C4 in IgE/Ag-stimulated BMMC through inhibition of FcɛRI-mediated Syk-dependent signal pathway.	(Li et al., 2015)
Salvia plebeia R. Brown	Whole plant	Aqueous extract	–	In vivo	No anaphylactic death occurred in compound 48/80-induced rats with intraperitoneal administration of 0.5 and 1 g/kg extract. At doses ranging from 0.01–1 g/kg, intraperitoneal and oral administration of extract showed with dose-dependent inhibition of PCA reaction.	(Shin and Kim, 2002)
				In vitro	Concentration-dependent reduction histamine release from RPMC activated by compound 48/80 or anti-DNP IgE at a concentration range of 0.001–1 mg/ml. TNF-α production from RPMC was significantly inhibited at concentrations of 0.01–1 mg/ml whereas cAMP level in RPMC significantly elevated compared with that of basal cells.	(Shin and Kim, 2002)
	Whole plant	Ethanol extract	–	In vivo	Oral administration of 100 mg/kg extract significantly suppressed serum IgE level, serum histamine, eosinophil count, pro-inflammatory cytokines (IFN-γ and TNF-α) expression, TH1, TH2 and TH17 cytokines expression in Der f-sensitized mice.	(Choi et al., 2014)
Schizonepeta tenuifolia (Benth.) Briq.	Whole plant	Aqueous extract	–	In vivo	100% protection from systemic anaphylaxis was observed with doses of 0.5 and 1 g/kg in compound 48/80-challenged rats whereas a marked suppression in PCA reaction was seen in orally administered of 0.1 and 1 g/kg of anti-DNP IgE-sensitized rats.	(Shin et al., 1999)
				In vitro	Significant inhibition of compound 48/80 or IgE-mediated histamine release from RPMC was marked at concentration range of 0.01–1 mg/ml. A potent inhibition of TNF-α production observed at 1 mg/ml with a content of 0.889 ± 0.747 ng/ml.	(Shin et al., 1999)
	Whole plant	Extract with phosphate buffered saline/olive oil (P/O) in proportion of (9:1) mixture	–	In vivo	Skin thickening and hyperplasia of epidermis and dermis in DNCB-sensitized mice remarkably decreased by 38.15% and 42.37% respectively with treatment of 1% of extract in P/O (9:1) mixture.	(Choi et al., 2013)
				In vitro	DNCB-induced mice observed with reduced serum levels of IgE, TNF-α and IL-6, recorded with 46.26%, 41.97% and 70.42% inhibition respectively with the treatment of 1% of extract in P/O (9:1) mixture.	(Choi et al., 2013)
	–	Aqueous extract	–	In vitro	Pro-inflammatory cytokines (IL-6, IFN-γ and TNF-α) and pro-allergic TH2 cytokines (IL-4 and IL-13) in RBL-2H3 were decreased with the treatment of 100 µg/ml of aqueous extract. β-hexosaminidase release from RBL-2H3 cells reduced significantly at dose of 10 µg/ml.	(Lin et al., 2018)
Scutellaria baicalensis Georgi	Roots	Wogonin (10), Ganhuangenin (11), Wogonoside (12), 3,5,7, 2’,6’-pentahydroxyflavanone (13)	Flavonoid	Ex vivo	(10), (11) and (12) significantly inhibited the production of IgE from concanavalin A-stimulated rat spleen lymphocytes at concentrations of 10.0 and 100.0 µM. Histamine and leukotriene B4 release from rat PEC was markedly suppressed at dose of 100 µM for all flavonoids.	(Lim, 2003; Lim et al., 2003)
	Roots	Aqueous extract	–	In vivo	Oral administration of 50 mg/kg extract selectively inhibited the release of IL-5 in mice.	(Kim et al., 2010)
	Roots	Baicalin (46)	Flavone glycoside	In vitro	Histamine and leukotriene release from OVA-sensitized guinea pig lung mast cells were potently suppressed at doses of 10, 30 and 60 µg. The standardized extract of (46) exhibited a more potent outcome than pure (46) at 60 µg only.	(Kim et al., 2010)
	Whole plant	Ethanolic extract	–	In vivo	Exhibited 6.6% inhibition of PCA reaction in sensitized-rats at 280 mg/kg.	(Jung et al., 2012)
				In vitro	40% reduction of histamine content in compound 48/80-stimulated RPMC with dose of 10 µg/ml. Significant reduced production of TNF-α and IL-8 in PMACI-stimulated HMC-1 cells with inhibition of MAPK activation at concentration range of 1–100 µg/ml.	(Jung et al., 2012)
	Roots	Aqueous extract	–	In vivo	Topical application of 5% extract reduced DNFB-induced cutaneous reaction by 31% as compared to control group.	(Kim et al., 2013)
				In vitro	Significantly suppressed β-hexosaminidase release from RBL-2H3 at doses of 125, 250 and 500 ppm with percentage inhibition of 19%, 34% and 60% respectively.	(Kim et al., 2013)
	Whole plant	Crude ethanol extract	–	In vivo	OVA-sensitized mice were protected from food allergy anaphylactic death by 60% and observed with significantly suppression of OVA-specific IgE, IL-17, TH2 cytokines (IL-4, IL-5, IL-10, IL-13) and TH1 cytokines (IFN-γ and IL-12) with the treatment of 25 mg/kg of extract.	(Shin et al., 2014b)
	–	Wogonin (10), Baicalin (46), Baicalein (47)	Flavonoid	Ex vivo	(10) suppressed the production of TH2 cytokines (IL-4, IL-5, IL-10, IL-13) and IFN-γ without causing cytotoxicity in OVA-sensitized mice splenocytes at 50 µmol/ml as compared to (46) and (47).	(Shin et al., 2014a)
				In vivo	Oral administration of 1 mg/kg of (15) potently decreased the production of OVA-specific IgE, IL-5, IL-10 and IL-13 in sensitized mice.	(Shin et al., 2014a)
	Roots	Aqueous extract	–	In vivo	Attenuation of DNCB-induced epidermal thickness, leukocytes infiltration, serum IgE, IL-4, IFN-γ and TNF-α production in BALB/c mice skin.	(Kim et al., 2016)
	Root	Ethanol extract, acetone extract and ethyl acetate extract	–	In vivo	The highest inhibitory activity against 4-AP-induced allergic skin pruritus, histamine-induced paw swelling, ear PCA reaction, anaphylaxis ear swelling and total serum IgE level was seen with 1.42 g/kg of ethanol extract in sensitized mice.	(Li et al., 2014)
	Rhizome	Baicalin (46), Baicalein (47), Oroxylin A (14)	Flavonoid	In vivo	(46) which was orally administered metabolized into (47) and (14). Metabolite, (14) possessed a more potent anti-histamine activity, seen with significant reduced histamine-induced scratching behaviour and vascular permeability in sensitized mice at doses of 20 and 50 mg/kg.	(Trinh et al., 2010b)
				In vitro	Metabolite of (46), (14) remarkably inhibited the contraction of guinea pig ileum with IC50 value of 0.28 mmol/L.	(Trinh et al., 2010b)
	–	Oroxylin A (14)	Flavonoid	In vivo	Significantly reduced eosinophils infiltration in BALF and airway hyperresponsiveness in OVA-sensitized mice. Potent attenuation of serum IgE level, TH2 cytokines (IL-4, IL-5 and IL-13) production and NF-κB activation with oral administration of 15, 30 and 60 mg/kg.	(Zhou et al., 2016)
	Roots	Linoleic acid (50)	Fatty acid	Ex vivo	Significantly suppressed the production of IL-4, IL-5, IL-10 and IL-13 but enhanced secretion of IFN-γ and IL-12, resulted in TH1/TH2 balance at 50 µg/L.	(Jung et al., 2017)
	–	Baicalein (47)	Flavonoid	In vivo	(47) induced CD4+ FOXP3 + T cell differentiation in ovalbumin-sensitized mice at concentrations of <10 µmol/L without causing cell death.	(Bae et al., 2016)
Stachys riederi var. japonica Miq.	Whole plant	Aqueous extract	–	In vivo	Dose-dependent inhibition was resulted in the occurrence of systemic anaphylaxis at concentration range of 0.005–1 g/kg and significant reduction of PCA reaction at concentrations of 0.1 and 1 g/kg.	(Shin, 2004)
				In vitro	At doses of 0.1 and 1 mg/ml, a significant decrease release of histamine from RPMC and diminished secretion of TNF-α and IL-6 from HMC-1 cells.	(Shin, 2004)
Teucrium japonicum Houttuyn	Whole plant	Aqueous extract	–	In vivo	Serum histamine release was significantly reduced at 100 and 1,000 mg/kg, with 500 mg/kg as the effective dose that completely protected compound 48/80-induced mice from systemic anaphylaxis. At doses ranging from 1–1,000 mg/kg, a dose-dependent inhibition of PCA reaction was resulted in anti-DNP IgE-challenged mice.	(Kim et al., 2009)
				In vitro	Significant reduction of compound 48/80-induced intracellular calcium and downstream histamine release from RPMC was observed at 1 mg/ml. Gene expression of TNF-α was diminished dose-dependently at 0.01–1 mg/ml with the involvement of NF-κB in PMACI-stimulated HMC-1 cells.	(Kim et al., 2009)
Thymus vulgaris Linn.	Leaves	2-isopropyl-5-methylphenol (15)	Monoterpenoid phenolic	In vivo	Dose-dependently inhibited recruitment of inflammatory cells, reduced airway hyperreponsiveness, suppressed level of OVA-specific IgE, TH2 cytokines in BALF at concentrations of 4, 8 and 16 mg/kg.	(Zhou et al., 2014)
	Leaves	n-hexane extract	–	In vivo	Portrayed intermediate inhibitory activity on histamine release with 46.22 ± 0.08%.	(Ikawati et al., 2001)
	–	2-isopropyl-5-methylphenol (15), Carvacrol (51)	Monoterpenoid phenolic	In vivo	(15) and (51) reduced delayed-type hypersensitivity by 26% and 50% respectively in ovalbumin-sensitized mice.	(Gholijani and Amirghofran, 2016)
				Ex vivo	Both compounds led to reduction of IL-2, IFN-γ, IL-4, IL-17 level and T-bet expression but increased level of IL-10 and TGF-β in mice splenocytes cultures.	(Gholijani and Amirghofran, 2016)
Vitex negundo Linn.	Leaves	Aqueous subfraction of ethyl acetate fraction	–	In vitro	Mast cell stabilizing activity with 80.99 ± 0.7231% was observed in rat mesenteric mast cells at dose of 500 µg/ml.	(Patel and Deshpande, 2011)
	Leaves	5-hydroxy-3, 6, 7, 3’,4’-pentamethoxyflavone (52)	Flavonoid	In vivo	200 mg/kg extract demonstrated significant reduction of eosinophil count in BALF and serum bicarbonate level in egg albumin sensitized guinea pigs.	(Patel and Deshpande, 2013)
Vitex rotundifolia Linn.	Fruits	Aqueous extract	–	In vivo	Dose-dependent reduction of systemic anaphylaxis reaction in compound 48/80-induced rats across concentration range of 0.0001–1 g/kg. Significant suppression of PCA reaction marked at doses of 0.5 and 1 g/kg in sensitized rats.	(Shin et al., 2000)
				In vitro	Histamine release from RPMC was reduced in a dose-dependent manner at dose range of 0.001–1 mg/ml and marked inhibition of TNF-α production at 0.001 mg/ml.	(Shin et al., 2000)
	Fruits	1H,8H-pyrano[3,4-c]pyran-1,8-dione (16)	Pyran	In vivo	Serum IgE, eosinophil counts and IL-5 production in BALF were significantly suppressed by 43%, 82% and 34% respectively. IL-4 and IL-5 level significantly decreased in CD4+ T cells in TH2 skewed condition with treatment.	(Lee et al., 2009)
				In vitro	Eosinophil migration and eotaxin production were reduced by 48% and 70% respectively at 10 µg/ml in A549 cell media.	(Lee et al., 2009)
	Fruits	Casticin (53)	Flavonoid	In vitro	Up to 63% of eosinophil migration inhibition was observed in A549 cell media with pretreatment of 10 µg/ml. Eotaxin level was reduced from concentration range of 0.1–10 µg/ml in A549 cells.	(Koh et al., 2011)
	–	Aqueous extract	–	In vivo	Oral administration of 100 mg/kg extract caused 86% inhibition of eosinophilia, reduction of TH2 cytokines (IL-4, IL-5, IL-13) and TNF-α level in BALF and decreased serum IgE level in ovalbumin-sensitized mice.	(Bae et al., 2013)
Vitex trifolia Linn.	Leaves	n-hexane and ethanolic extract	–	In vitro	Both n-hexane and ethanolic extract highly suppressed histamine release by 80.13 ± 3.95 and 81.58 ± 0.24% respectively in RBL-2H3 cells.	(Ikawati et al., 2001)
	Leaves	Viteosin-A (48), Vitexicarpin (49)	Flavonoid	Ex vivo	(48) and (49) respectively reduced histamine-induced tracheal contraction by 27.1% and 66.2% at 0.00013 M and percentage increased to 47.9% and 97.2% respectively when raised to 0.0004 M.	(Alam et al., 2002)
Zataria multiflora Boiss.	Whole plant	Hydro-ethanolic extract	–	In vitro	Observed with increment of Treg cells, TH1/TH2 ratio, IFN-γ/IL-4 ratio, IFN-γ and FOXP3 expression. Significant reduction of TH2 and TH17 cells and decreased expression of IL-4, IL-17 and TGF-β occurred in sensitized mice spleen cells.	(Kianmehr et al., 2017)
	Seeds	Hydro-ethanolic extract	–	In vivo	Increased IFN-γ and decreased IL-4 were resulted in ovalbumin-sensitized guinea pigs with the oral administration of extract.	(Boskabady et al., 2013)
				In vitro	Achieved TH1/TH2 balance with enhanced ratio of IFN-γ/IL-4 in PHA-stimulated hPBMC.	(Boskabady et al., 2013)