Table 4.

The neuroprotective effects compounds of Traditional Chinese medicines on animal models post-TBI

Compounds of Traditional Chinese medicines	Subordinate herb	Models	Species	Gender	Sample size	Mode of action	Effects on post‐TBI consequences
Ginsenoside Rg1 [67]	P. Ginseng	WDI	Rat	Male	48	↓ Exos-miR-21, MMP1/3/9, ↑TIMP3, VEGF, GFAP and p-P65/P65, ZO-1,occludin and claudin-5	↓ cerebrovascular endothelial injury
Ginsenoside Rb1 [68]		CCI	Rat	Male	36	↑ p-ERK1/2; ↓connexin40	↓ brain water content
Crocin [69]	C. tinctorius	CCI	Mouse	Male	150	↑ GSH, ↓ IFN-γ, TNF-α, MPO and MDA	↑anti-inflammatory and anti-oxidative effects; ↑ cognitive function
Panax Notoginseng Saponins [72]	Panax notoginseng	WDI	Rat	Male	45	↑ PI3K/Akt/mTOR, Bcl-2; ↓ Bax	↓ apoptosis cells
Gastrodin [75]	Gastrodia elata	WDI	Rat	Male	30	↓GSDMD, NLRP3, ASC, caspase-1,caspase-11 and IL-18	↓ pyroptosis
Rhein [79]	Rheum palmatum	WDI	Mouse	Male	44	↓ LDH, GSDMD, NLRP3, TLR4, MyD88, IL-1β, IL-18 and IFN-γ; ↑p10, p20 and p45	↑ cognitive function; ↓ pyroptosis
Emodin [80]		WDI	Rat	Male	50	↓ NF-κB p65, ICAM-1, S100B, IL-6 and TNF-α; ↑ Nrf2	↑ cognitive function
Ginkgolide B [82]	Ginkgo biloba	WDI	Rat	Unknown	30	↓ Omi/Htr A2, procaspase-3/9, cleaved PARP, XIAP	↓ apoptosis cells;↓ brain edema
Resveratrol [83–85]	P.cuspidatum	WDI	Mouse	Male	72	↓P-p38 MAPK; ↑ Sirtuin 1 and SYN	↑neurological function
		WDI	Mouse	Male	42	↑PGC-1, Sirtuin1and SYN	↑ cognitive function
		CCI	Rat	Male	150	↑P62,P-pI3K, P-Akt and P-mTOR; ↓LC3 II and Beclin-1	↓ brain edema; ↑ cognitive function
Curcumin [87-90]	C. longa	WDI	Rat	Male	36	↑ GFAP, DCX, Map2; ↓CD68	↓ brain lesion, apoptosis cells
		WDI	Mouse	Male	30	↓ROS, CXCL1, TNF-α, IL-1β, IL-6; ↑GAP43, doublecortin	↑cognitive function
		WDI	Mouse	Male	68	↓p-p38, NF-κB, IL-1β, IL-6 and TNF-α; ↑IL-10	↑neurological function; ↓inflammatory response
		CCI	Rat	Male	145	↑ BNDF, Trkb, PI3K and AKT;↑BrdU	↑ neurogenesis, spatial memory; ↓ inflammation
Salvianolic acid A [94]	S. miltiorrhiza	CCI	Mouse	Male	20	↓ TNF-α,IL-6,IFN-b,TLR2 and TLR4, NMDAR, PINK1,↑NMNAT1	↓ apoptosis
Tanshinone IIA [95]		WDI	Rat	Male	72	↓ p47phox, CD11, AQP4, GFAP, MDA, CAT, IL-1β, and TNF-α; ↑SOD and GSH-PX	↓brain edema,inflammation
Artesunate [96, 97]	A. annua	CCI	Mouse	Male	40	↓ Nf-kb, inflammation body complex, GFAP and Iba-1; ↑BDNF, GDNF and NT-3	↓inflammation
		CCI	Rat	Male	30	↓ GSK-3β; ↑occludin, ZO-1 Phosphorylation of Akt	↓ brain water content and neuroinflammation

TIMP3 tissue Inhibitors Of metalloproteinase 3, PI3K Phosphoinositide 3-kinase, GSDMD Gasdermin D, ASC apoptosis-related macular protein of the adapter protein containing CARD, NLRP3 NOD-like receptor protein 3, ICAM-1intercellular cell adhesion molecule-1, VEGF vascular endothelial growth factor, GFAP glial fibrillary acidic protein, XIAP X-linked inhibitor of apoptosis protein, LC-3II microtubule-associated-proteinlight-chain-3II, SYN synaptophysin, Trkb tropomyosin receptor kinase B