. 2022 Jun 6;19:132. doi: 10.1186/s12974-022-02492-0

Table 2.

Plant-derived natural compounds and formulations that regulate microglia-mediated neuroinflammation in animal models of depression

Treatment	Animal models	Behavioral test	Analyzed regions	Microglia	Pro-inflammation	Anti-inflammation
Crocin [226]	LPS	OFT, FST, TST, FST	HIP	—	ELISA: IL-1β, IL-18, TNF-α ↓ Proteins: CD16/32, iNOS, p-65-NF-κB ↓	Protein: CD206 ↑
Baicalin [186]	CMS	OFT, FST, TST, FST	HIP	—	Proteins: IL-1β, IL-6, TNF-α, TLR4 ↓	—
Catalpol [205]	CMS	OFT, EPM, FST	HIP	Iba-1⁺↓	mRNA: IL-1β, TNF-α, iNOS, IL-6, CD206 ↓ Proteins: NLRP3, cleaved caspase-1, IL-1β ↓ ROS ↓	mRNA: CD206 ↑
Ganoderic acid A [227]	MCAO + CMS	OFT, SPT	HIP	—	ELISA: TNF-α, IL-1β, IL-6 ↓ mRNA: TNF-α, IL-1β, IL-6, iNOS, CD68 ↓ Proteins: iNOS, CD68 ↓	ELISA: IL-10 ↑ mRNA: IL-10, CD206, Arg-1 ↑ Proteins: CD206, Arg-1 ↑
Ginsenoside Rb1 [73]	CMS	OFT, SPT, TST, FST	HIP	Iba-1⁺↓	mRNA: TNF-α, IL-1β ↓	mRNA: TGF-β, Arg-1 ↑
Ginsenoside Rb1 [73]	CMS	OFT, SPT, TST, FST	Cortex	Iba-1⁺↓	mRNA: TNF-α, IL-1β ↓	mRNA: TGF-β, Arg-1 ↑
Salvianolic acid B [213]	CMS	SPT, TST, FST	HIP	Iba-1⁺(–)	ELISA: TNF-α ↓ mRNA: IL-1β, TNF-α ↓	ELISA: IL-10 ↑ mRNA: IL-10, TGF-β ↑
Salvianolic acid B [213]	CMS	SPT, TST, FST	Cortex	Iba-1⁺↓	ELISA: TNF-α ↓ mRNA: IL-1β, TNF-α ↓	ELISA: IL-10 ↑ mRNA: IL-10, TGF-β ↑
Curcumin [215]	GWI + CRS	OLT, NORT, NSFT	HIP	Iba-1⁺↓	—	—
Ginsenoside Rb1 [197]	CRS	OFT, TST, FST	HIP	Protein: Iba-1 ↓	Proteins: TNF-α, IL-1β ↓	—
Arctigenin [171]	CMS	SPT, TST, FST	Serum	—	ELISA: TNF-α, IL-1β, NO ↓	—
Arctigenin [171]	CMS	SPT, TST, FST	PFC	Iba-1/HMGB1⁺↓ Protein: Iba-1 ↓	Proteins: TNF-α, IL-1β, IDO ↓	—
Astragalin [231]	CMS	SPT, TST, FST	HIP	Iba-1⁺↓	Proteins: Nuclear p65-NF-κB, NLRP3, cleaved caspase-1, cleaved IL-1β, cleaved gasdermin D ↓	—
Saikosaponin-d [190]	LPS	OFT, FST, TST, FST	HIP	Iba-1⁺↓ in CA1	Proteins: CD68, IL-1β, IL-6, TNF-α, HMGB1, TLR4, p65-NF-κB, p-IκB-α ↓	—
Asperosaponin VI [228]	LPS	OFT, FST	HIP	Iba-1⁺↓	mRNA: IL-1β, IL-6, TNF-α, iNOS ↓ Proteins: IL-1β, TNF-α, TLR4, p-NF-κB/NF-κB ↓	—
Asperosaponin VI [228]	LPS	OFT, FST	PFC	Iba-1⁺, iNOS/ Iba-1⁺↓	mRNA: IL-1β, IL-6, TNF-α, iNOS ↓ Proteins: IL-1β, TNF-α, TLR4, p-NF-κB/NF-κB ↓
5-O-Methylvisammioside [233]	LPS	OFT, FST, FST, EPM	HIP	—	Proteins: NF-κB, IκB-α ↓	—
Scutellarin [230]	LPS	OFT, SPT, FST	HIP	Iba-1⁺↓	Proteins: NLRP3, caspase-1, IL-1β ↓ ROS ↓	—
Ginsenoside Rg1 [200]	CMS	SPT, FST	vmPFC	Iba-1⁺↓	mRNA: IL-1β, IFN-γ, TNF-α ↓ ELISA: IL-1β, IFN-γ, TNF-α ↓	—
Ginsenoside Rg3 [201]	LPS	—	Cortex	Iba-1⁺↓	—	—
			Hypothalamus	Iba-1⁺↓	—	—
			Brain	iNOS⁺, COX-2⁺, Iba-1⁺↓	mRNA: IL-1β, IL-6, TNF-α	—
Magnolol [219]	CMS	OFT, SPT, FST, TST	HIP	Iba-1⁺↓ in DG; Iba-1/CD16/32⁺↓, Iba-1/CD206⁺↑	—	—
Magnolol [219]	CMS	OFT, SPT, FST, TST	Brain	—	ELISA: TNF-α, IL-1β, IL-6, IL-12 ↓	ELISA: IL-4, IL-10 ↑ mRNA: Arg1, Ym1, Fizz1, Klf4 ↑
Geniposide [208]	LPS	SPT, TST, FST, OFT	HIP	—	ELISA: TNF-α, IL-6 ↓ Proteins: CD86 ↓, CD206 ↑	—
Geniposide [208]	LPS	SPT, TST, FST, OFT	Serum	—	ELISA: TNF-α, IL-6 ↓	—
Arctiin [210]	CMS	TST, FST, OFT, SPT	PFC	Iba-1⁺/HMGB1⁺↓ Protein: Iba-1 ↓	Proteins: TNF-α, IL-1β, iNOS, HMGB1 ↓	—
Arctiin [210]	CMS	TST, FST, OFT, SPT	Serum	—	ELISA: TNF-α, IL-1β, iNOS ↓
Ginkgolide B [234]	Depression in post myocardial infarction	OFT, SPT	Median raphe nucleus	—	ELISA: IL-1β ↓ mRNA: IL-1β ↓	—
			HIP	Iba-1⁺↓	ELISA: IL-1β ↓ mRNA: IL-1β ↓	—
			Cortex	—	ELISA: IL-1β ↓ mRNA: IL-1β ↓	—
Leonurine [235]	CMS	TST, FST, SPT	HIP	—	Proteins: IL-1β, IL-6, TNF-α, p-IKKβ/IKKβ, p-p65/p65 ↓	—
Hesperidin [232]	CMS	FST, SPT, OFT	PFC	Iba-1⁺↓	mRNA: NLRP3, caspase-1, ASC ↓ Proteins: NLRP3, caspase-1, ASC ↓ ELISA: IL-1β, IL-6, TNF-α ↓	—
20(S)-Protopanaxadiol [229]	CMS	SPT, TST, FST	HIP	Iba-1⁺↓	Proteins: iNOS, COX-2, acetylated p65 (ac-p65) ↓	—
20(S)-Protopanaxadiol [229]	CMS	SPT, TST, FST	Cortex	Iba-1⁺↓	—	—
Ferulic acid [236]	CMS	SPT, FST	PFC	—	mRNA: IL-6, IL-1β, TNF-α, NF-κB, CD11b ↓ Proteins: NLRP3, caspase-1 ↓	—
Resveratrol [224]	LPS	OFT, TST, FST	HIP	Iba-1⁺↓ in DG-SGZ	—	—
(+)-Sesamin [69]	CMS	OFT, FST, TST, EMP	HIP	Protein: Iba-1 ↓	mRNA: COX-2, iNOS, IL-1β, TNF-α ↓	—
(+)-Sesamin [69]	CMS	OFT, FST, TST, EMP	Prelimbic cortex	Protein: Iba-1 ↓	mRNA: COX-2, iNOS, IL-1β, TNF-α ↓	—
Quercetin [187]	OBX	OFT, FST	HIP	—	ELISA: TNF-α, IL-6 ↓	—
Quercetin [187]	OBX	OFT, FST	Cortex	—	ELISA: TNF-α, IL-6 ↓	—
Theaflavins [246]	LPS	TST	HIP	MIP-1α/CD11b⁺, TNF-α/CD11b⁺↓ in microglia	ELISA: TNF-α, IL-1β ↓	—
Epigallocatechin-3-gallate [99]	LPS	—	HIP	Iba-1⁺↓ in DG	mRNA: IL-1β, IL-6, TNF-α ↓ Proteins: TLR4, Rel A, pRel A ↓ ELISA: IL-1β, IL-6, TNF-α ↓	—
Gypenosides [192]	CMS	SPT, TST	HIP	Iba-1⁺↓ in DG	mRNA: IL-6 ↓ Proteins: IL-6, TNF-α ↓	—
Kososan [237]	CSDS	Social avoidance test	HIP	Iba-1⁺↓	—	—
Aquilariae Lignum ethanol extracts [238]	CRS	—	HIP	Iba-1⁺↓	Proteins: TNF-α, IL-1β, iNOS ↓	—
Rosemary Extracts [239]	CRS	OFT, TST, FST	Serum	—	ELISA: IL-1β, TNF-α ↓	—
Rosemary Extracts [239]	CRS	OFT, TST, FST	HIP	Protein: Iba-1 ↓	Proteins: IL-1β, TNF-α, p-p65-NF-κB ↓	—
Radix Polygalae extract [240]	CRS	OFT, SPT, NSFT	PFC	Iba-1⁺↓	mRNA: NLRP3, IL-1β, IL-6, IL-18, TNF-α ↓ Proteins: NLRP3, ASC, cleaved caspase-1	—
Bangpungtongsung-san [241]	Reserpine	OFT, TST, FST	HIP	—	mRNA: IL-1β, IL-6, TNF-α ↓	—
XingnaoJieyu decoction [242]	MCAO + CMS	OFT, FST	Cortex	Iba-1⁺↓	ELISA: TNF-α, IL-6, IL-1β ↓	—
XingnaoJieyu decoction [242]	MCAO + CMS	OFT, FST	HIP	Iba-1⁺↓	ELISA: TNF-α, IL-6, IL-1β ↓	—
Ganoderma lucidum polysaccharides [243]	CSDS	OFT, SPT, TST, FST	HIP	Iba-1⁺↓	Proteins: IL-1β, TNF-α ↓	Proteins: IL-10, BDNF ↑
Water extract of Armillaria mellea (Vahl) P. Kumm [244]	CMS	OFT, FST	Cerebral	Protein: Iba-1 ↓	Proteins: IL-1β, TNF-α ↓	—
Xiaoyaosan [245]	CMS	SPT, OFT, FST, NSFT	HIP	Iba-1⁺↓	mRNA: COX-2 ↓	—
Myelophil [96]	CMS	OFT, TST, FST	HIP	Iba-1⁺↓ in CA1, DG, CA3	ELISA: IL-1β, TNF-α ↓ Proteins: NLRP3, ASC, pro-IL-1β, IL-1β ↓	—

↑upregulated; ↓downregulated; (–) no significant difference;—no explicit data