Potential Role of Natural Plant Medicine Cyclocarya paliurus in the Treatment of Type 2 Diabetes Mellitus

Table 1

Potential role of the major compounds and extracts of C. paliurus in T2DM and its complications.

Chemical compound/extract	Method of extraction	Model for the experiments	Effect	Potential mechanism	References
Polysaccharide	Water extraction	Male Wistar rats	Regulation of gut microbiota	UCG-005, SCFAs↑; IL-1β, IL-6, TNF-α↓; Leptin↓, adiponectin, GLP-1↑; Bcl-2↑, Bax↓	[66]
	Ethanol extraction	Sprague-Dawley rats	Regulation of gut microbiota	SCFA-producing bacteria↑; mRNA in GPR41, GPR43, GPR109a↑; SCFA-GLP1/PYY associated sensory mediators↑	[72]
	Ethanol extraction	Sprague-Dawley rats	Hypolipidemic	FAS, HMG-CoA↓, ATGL, PPAR↑	[79]
	Ethanol extraction	Sprague-Dawley rats	Hypolipidemic	DNA methylation of leptin and MTTP↓, mRNA contents of leptin and MTTP↓	[80]
	Hot water extraction	RAW264.7 cell	Anti-inflammatory	Accounted for synergistic effect on the release of NO and TNF-α, accounted for antagonistic effect on the release of IL-1β and PGE2.	[50]
	Hot water method assisted by ultrasonic	Female ICR mice	Hypolipidemic	The expression of ATGL and PPARα gene in liver↓, high expression level of fatty acid synthesis gene induced by HFD↓, SOD, GSH-PX, GPT, T-AOC↑, LPO, MDA↓	[13]
	Water extraction	Kunming mice	Regulation of gut microbiota	SCFAs↑, diversity of the intestinal flora↑, specific metabolic functions of the gut microbiota↑	[20]
	Water extraction	C. elegans	Hypolipidemic	Size distribution of lipid droplets↓, number of lipid droplets↓, through MUFA biosynthetic pathways, MDT-15/sbp-1 and NHR-49/MDT-15 signaling pathway	[82]
	Ethanol extraction	Kunming mice	Antioxidant	Induction of CYP2E1 expression in liver by CCl4↓, ROS↓, SOD, GSH-Px↑, MDA↓	[58]
	Water extraction	C. elegans	Antioxidant	ROS, MDA, NEFA, GSSG↓, SOD, CAT, GSH-Px, GSH↑	[57]
	Water extraction	Kunming mice	Anti-inflammatory	NO, iNOS, COX-2, TNF-α and IL-1β↓, SCFAs↑, TLR4 protein expression↓, ERK, JNK p38↓	[7]
Triterpenoid	Ethanol extraction	C57BL/6J mice, HepG2 cells	Ameliorate of insulin resistance	Upregulation of PI3K/Akt/GSK3βpathway	[34]
	Ethanol extraction	db/db mice, HepG2 and LO2 cells	Anti-inflammatory	IL-6, IL-1β, TNF-α↓,; hepatic expression of Rho-kinase and NF-κB↓	[51]
	Ethanol extraction	Mouse C2C12 myoblasts and 3T3-L1 preadipocytes	Improve glucose uptake	Activate AMPK-p38 pathway,; Insulin sensitivity of adipocytes↑	[41]
	Ethanol extraction	Male Sprague-Dawley rats	Attenuates kidney injury	AMPK phosphorylation↑, mTOR phosphorylation↓	[96]
	Ethanol extraction	Male Sprague-Dawley rats	Hypolipidemic	Inhibition of intestinal apoB48 production through TNF-α/p38 MAPK signaling pathway,; MDA↓, GSH-P, SOD, CAT↑	[85]
	Ethanol extraction	3T3-L1 adipocytes	Promote glucose uptake in 3T3-L1 adipocytes	AMPK activation↑, IKKβ phosphorylation in adipocytes↓, restored insulin-mediated phosphorylation of IRS-1 tyrosine and Akt	[42]
	Ethanol extraction	FFA-induced HepG2 steatosis cells	Antioxidant	SOD↑, MAD↓	[59]
	Ethanol extraction	RAW 264.7 cells	Anti-inflammatory	NO, TNF, PGE2, IL-6↓, COX-2, iNOS, NF/p65↓	[48]
	Ethanol extraction	RAW264.7 cell	α-Glucosidase inhibitory and anti-inflammatory	mRNA expression of iNOS, COX-2, NF-κB, IL-6, IL-1β, and TNF-α↓, protein expression of iNOS, NF-κB/p65 and COX-2↓	[49]
Flavonoid	Hot water extraction	Male C57BL/6 J mice	Regulation of gut microbiota	Faecal microbiota diversity↑, Bacteroidetes↑, Firmicutes, Proteobacteria↓	[65]
	Ethanol extraction	RAW264.7 cell	Inhibit XOD activity, inhibition of NO production in LPS induced RAW264.7 cells	Not mentioned	[32]
Extract	Ethanol/chloroform extraction	KM male mice	Hypolipidemic	CYP7A1↑, HMG-CoA reductase↓	[83]
	Water extraction	Male Wistar albino rats	Alleviates diabetic nephropathy	Reduce oxidative stress, suppress the activation of the polyol pathway through aldose reductase inhibition	[14]
	Ethanol extraction	Kunming mice	Hypolipidemic	TNF-α, mRNA↓, p38 phosphorylation↓, inhibit MAPK signaling along the TNF-α/p38MAPK pathways	[84]
	Ethanol/water extraction	SD male rats	Antioxidant	MDA↓, SOD, GSH-Px↑	[93]
	Hot water extraction	Male C57/BL6J mice	Inhibit β cell apoptosis	Caspase-8, caspase-9, cleaved caspase-3↓, Bax/Bcl-2↓, p38, ERK and JNK phosphorylation↓, Akt phosphorylation↑	[74]
	Ethanol extraction	HepG2 cells	Attenuates hepatic lipid deposition	p-mTOR↓, Beclin↑, p-p70S6K↓, p62↓	[40]
	Water extraction	SHR/cp rats	Improving insulin signaling in the hypothalamus	m-PI3Kp85↑, p-Akt↑, p-FoxO1↑, POMC↑, NPC↓	[11]
	Ethanol extraction	db/db mice	Protect against diabetic cardiomyopathy	TNF-α, IL-1β, IL-6↓, Bcl-2↑, cle-caspase-3, cle-caspase-9, Bax↓	[100]
	Hot water extraction	Male Sprague-Dawley rats	Ameliorate diabetes	SOD↑, MDA↓, Ins1, Ins2↑, β-cell mass↑, Ddit4, Fgf21↑, DNA replication↑, cytochrome P450↓	[52]