Combining acupuncture and mesenchymal stem cell therapy offers promise as a treatment for inflammatory bowel disease

Table 1 Antioxidant and anti-inflammatory mechanisms of mesenchymal stem cell

Ref.	Model	Cell type	Method	Mechanism indicators	Pathway
Che et al[55]	LPS-treated mice	hUC-MSC	Tail vein injection	TNF-α↓; IL-6↓; ROS↓; CD86↓; CD206↑; NLRP3↓; ASC↓; caspase-1↓	Nrf2/NF-κB/NLRP3
Cao et al[56]	SCI mice	hUC-MSC	Injected along the spinal cord	TNF-α↓; PTBP1↓	TNF-α/NF-κB
Stavely et al[58]	IBD mice	BM-MSC	Enema	IL-6↓; TNF↓; IL-1α↓; IL-1b↓; IFNG↓; CXCL2↓; TBX21↓; ITGAM↓; NOS2↓; ARG1↓; GATA3↓; MRC1↓; HMOX1↓; FOXP3↑; CD45↓	-
Xian et al[146]	SE mice	MSC-Exo	Intraventricular injection (in vivo), mix culture (in vitro)	GFAP↓; C3↓; CD81↓; Ki67↓; TNF-α↓; IL-1β↓	Nrf2/NF-κB
Xiao et al[147]	ALI mice	BM-MSC	Tail vein injection	Ikbkb↓	NF-κB/hedgehog
Zhang et al[148]	IBD mice and CIA mice	hUC-MSC	Tail vein injection	Tregs↑; Th17↓	ETS2/AURKA/NF-κB/Fas/MCP-1
Li et al[149]	ALI mice	BM-MSC	In vitro MSC isolation	TNF-α↓; IL-6↓; IL-10↓; HO-1↑; GPX-1↑	Nrf2/ARE and NF-κB
Song et al[150]	ADR induced nephropathy mice	BM-MSC	Tail vein injection	MDA↓; IL-10↓; IFN-γ↓; TNF-α↓; IL-12↓; COX-2↓	NF-κB
Han et al[151]	SAH rats	BM-MSC	Tail vein injection	TGFβ↑; iNOS↓; CD16↓; CD11b↓; IL-1β↓; p-AMPK↑	AMPK/NF-κB
Wang et al[152]	SCI rats	MSC-Exo	Intrathecal injection	TNF-α↓; IL-1β↓; IL-6; Bcl2↓; Bax↓; caspase-3↓	miR-146b/TLR4/NF-κB p65

LPS: Lipopolysaccharide; hUC-MSC: Human umbilical cord mesenchymal stem cell; TNF: Tumor necrosis factor; IL: Interleukin; ROS: Reactive oxygen species; NLPR3: NOD-like receptor family pyrin domain-containing 3; ASC: Apoptosis-associated speck-like protein; Nrf2: Nuclear factor erythroid 2-related factor 2; NF-κB: Nuclear factor-kappa B; NLRP3: Nod-like receptor protein 3; SCI: Spinal cord injury; PTBP1: Polypyrimidine tract-binding protein 1; IBD: Inflammatory bowel disease; BM-MSC: Bone marrow mesenchymal stem cell; IFNG: Interferon gamma; CXCL2: CXC motif chemokine ligand 2; TBX21: T-box transcription factor 21; ITGAM: Integrin Subunit α M; NOS2: Nitric oxide synthase 2; ARG1: Arginase 1; GATA3: GATA binding protein 3; MRC1: Mannose receptor C-type 1; HMOX1: Heme-oxygenase 1; FOXP3: Forkhead box protein 3; SE: Status epilepticus; MSC-Exo: Mesenchymal stem cell derived exosome; GFAP: Glial fibrillary acidic protein; ALI: Acute lung injury; Ikbkb: Inhibitor of nuclear factor kappa B kinase subunit B; CIA: Collagen-induced arthritis; Treg: Regulatory T cell; Th17: T helper type 17 cell; ETS2: ETS proto-oncogene 2, transcription factor; AURKA: Aurora kinase A; MCP-1: Monocyte chemoattractant protein-1; MSC: Mesenchymal stem cell; HO-1: Heme oxygenase-1; GPX-1: Glutathione peroxidase 1; ARE: Antioxidant response element; ADR: Antioxidant response element; MDA: Malondialdehyde; IFN: Interferon; COX-2: Cyclooxygenase 2; SAH: Subarachnoid hemorrhage; TGF: Transforming growth factor; iNOS: Inducible nitric oxide synthase; AMPK: AMP-activated protein kinase; TLR4: Toll-like receptor 4.

Table 2 Antioxidant and anti-inflammatory mechanisms of acupuncture

Ref.	Model	Intervention	Acupoints	Acupoint stimulation parameters	Mechanism indicators	Pathway
Zhang et al[86]	IBD mice	EA	Bilateral: BL25	EA: 2 Hz, 1 mA, 30 minutes, 7 days	IL-1β↓; iNOS↓; CD68↓	-
Song et al[90]	UC mice	EA	ST36	EA1: 100 Hz, 1 mA, 30 minutes, 7 days; EA2: 10 Hz, 1 mA, 30 minutes, 7 days	IL-1β↓; IL-6↓; IL-12↓; TNF-α↓; IL-17↓; IL-10↑	-
Zhou et al[95]	PTSD mice	EA	Pretreatment	EA: 2/15 Hz, 1 mA, 30 minutes, 7 days	BDNF↓; AMPK↓; HO-1↓	AMPK/Nrf2; Keap1/Nrf2
Yu et al[96]	ALI rabbits	EA	Bilateral: ST36; BL13	EA1: 2/15 Hz, ≤ 1 mA, 15 minutes, 5 days; EA2: 2/15 Hz, ≤ 1 mA, 6 hours, 1 days	MDA↓; SOD↑; GPX↑; TNF-α↓; IL-6↓; HO-1↑	Nrf2/ARE
Dai et al[153]	SCI mice	EA	Bilateral: ST36; SP6	EA: 60 Hz for 1.05 seconds and 2 Hz for 2.85 seconds, alternately; ≤ 5 μA	ApoE↑; TNF-α↓; IL-6↓; IL-1β↓; IL-10↑; TGF-β↑	Nrf2-HO-1; Nrf2/NQO1/HO-1
Li et al[154]	CIRI rats	EA	GV20, SP6, bilateral: ST36	EA: 2/15 Hz, 5 mA or 10 mA, 30 minutes, 5 days	TNF-α↓; HO-1↑; iNOS↓	Nrf2/HO-1
Wang et al[155]	VD mice	Acupuncture	GV20, bilateral: ST36	10 minutes needle retention	TNF-α↓; TLR4↓; IL-6↓	MyD88/NF-κB
Lou et al[156]	I/R rats	EA	Pretreatment: ST36; SP6	EA: 2/15 Hz, 1 mA	TNF-α↓; IL-1↓; IL-6↓; MPO↓; TLR4↓; p-NF-κB↓	TLR4/NF-κB
Wu et al[157]	UC rats	EA and HPM	EA: Bilateral ST25. HPM: (Qihai)RN6; bilateral (Tianshu)ST25	EA: 2 Hz, 4 mA, 20 minutes, 14 days; HPM: Moxa cones (refined mugwort floss)	IL-1β↓; IL-6↓	-
Liu et al[158]	UC mice	EA	Bilateral: ST36	EA: 2 Hz, 1 mA, 15 minutes, 7 days	IFN-γ↓; IL-6↓; TNF-α↓	TLR4/MyD88

IBD: Inflammatory bowel disease; EA: Electroacupuncture; IL: Interleukin; iNOS: Inducible nitric oxide synthase; UC: Ulcerative colitis; TNF: Tumor necrosis factor; PTSD: Post-traumatic stress disorder; BDNF: Brain-derived neurotrophic factor; AMPK: AMP-activated protein kinase; HO-1: Heme oxygenase-1; Nrf2: Nuclear factor erythroid 2-related factor 2; Keap1: Kelch-like ECH-associated protein 1; ALI: Acute lung injury; MDA: Malondialdehyde; SOD: Superoxide dismutase; GPX: Glutathione peroxidase; ARE: Antioxidant response element; SCI: Spinal cord injury; ApoE: Apolipoprotein E; TGF: Transforming growth factor; CIRI: Cerebral ischemia-reperfusion injury; VD: Vitamin D; TLR4: Toll-like receptor 4; NF-κB: Nuclear factor-kappa B; I/R: Ischemia/reperfusion; MPO: Myeloperoxidase; HPM: Herbs-partition moxibustion; IFN: Interferon; MyD88: Myeloid differentiation factor-88.