. 2022 Jan 13;12:783127. doi: 10.3389/fphar.2021.783127

TABLE 2.

Anti-diabetic, antimicrobial, antiprotozoal, and central nervous system activities and mechanisms of jatrorrhizine in in vitro and in vivo assays.

Effect	Assay	Cell lines/model	Dosage	Type of biological activity	References
Anti-obesity and hypolipidemic activity
	In vitro	HepG2 cells	15 μM	Increased LDLR expression and decreased cellular lipid accumulation	Zhou et al. (2014)
	In vivo	high-fat and high-cholesterol (HFHC)-induced hyperlipidemic hamsters	46.7 mg/kg	Decreased TC, TG, TBA and increased the fecal excretion of cholesterol; upregulation of LDLR, CYP7A1 and HMGCR	He et al. (2016)
	In vivo	C57BL/6 mice on a HFHC diet	20 mg/kg; 100 mg/kg	Decreased body weight, TC, TG, LDL-C, AST, ALT and increased HDL-C; amelioration of liver pathophysiological changes (swelling of hepatocytes and lipid accumulation); downregulation of SREBP-1c and FAS; upregulation of PPAR-α and CPT1A	Yang et al. (2016)
Anti-diabetic activity
	In vitro	RINm5F cells	20 μg/ml	Increased insulin secretion	Patel and Mishra (2011)
	In vitro	Rat hepatocytes	5–80 μg/ml	Inhibition of hepatic gluconeogenesis
	In vivo	Glucose-loaded rats	40 mg/kg	Increased insulin secretion and inhibition of hepatic gluconeogenesis
	In vitro	HepG2 cells	0.6 μM	Glucose-lowering effect	Chen et al. (2012)
	In vivo	Diabetes mellitus Wistar rats	50, 100 mg/kg	Reduced IL-1β, TNF-α and upregulation of p-AKT, p-AMPK, eNOS	Wang et al. (2017)
	In vitro	IR-3T3-L1 adipocytes	0.5, 1, 5, 10, 20 μmol/L	Amelioration of insulin resistance and upregulation of IRS2, PI3KR1, p-AKT, p-AMPK and GLUT4/1/2	Zhu et al. (2018)
	In vivo	Hyperlipidemia model mouse	100 mg/kg	Reduced the body weight and improved glucose tolerance and insulin sensitivity	Yang et al. (2016)
	In vitro	α-glucosidase	IC₅₀ = 36.25 μg/ml	Inhibitory activity against α-glucosidase	Patel and Mishra (2012b)
	In vivo	Wistar rats	20 mg/kg	Inhibitory activity against α-glucosidase	Patel and Mishra (2012b)
	In vitro	Lens AR isolated from Wistar rats	IC₅₀ = 3.23 mg/ml	Inhibitory activity against aldose reductase	Patel and Mishra (2012a)
Anti-microbial activity
	In vitro	Candida albicans SC5314	MIC = 256 μg/ml	Inhibitory activity against Candida albicans and Candida auris	Liu et al. (2020)
		Candida auris 12372	16 μg/ml in Candida albicans	Induced cell wall remodeling
		Candida auris 12372	64 μg/ml in Candida auris	Induced cell wall remodeling
	In vitro	Propionibacterium acnes coagulase-negative staphylococci Candida tropicalis	MIC of 25–50 μg/ml in Propionibacterium acnes	Inhibitory activity against Propionibacterium acnes, coagulase-negative staphylococci and Candida tropicalis	Slobodníková et al. (2004)
			MIC of 100–250 μg/ml in coagulase-negative staphylococci
			MIC of 125 μg/ml in C. tropicalis
	In vitro	Staphylococcus aureus SMRSA 106 and EMRSA 16	200 μg/ml	Inhibition of antibiotic resistant Staphylococcus aureus	Ali et al. (2013)
	In vitro	Staphylococcus aureus (MRSA) SA1199B	MIC = 64 mg/L	Inhibitory activity against methicillin-resistant Staphylococcus aureus	Yu et al. (2019)
	In vivo	Neutropenic murine thigh infection model	25 or 50 mg/kg of jatrorrhizine and 100 mg/kg of NFX		Yu et al. (2019)
	In vitro	Neuraminidase of Clostridium perfringens	IC₅₀ = 37.0 ± 1.8 μΜ	Inhibitory activity against bacterial NA	Kim et al. (2014)
Anti-protozoal activity
		Plasmodium falciparum K1	IC₅₀ = 0.24 ± 0.002 μg/ml	Anti-plasmodial, anti-trypanosomal and anti-leishmanial activity	Malebo et al. (2013)
		Trypanosoma brucei rhodesiense STIB 900	IC₅₀ = 4.2 ± 0.002 μg/ml
		Leishmania donovani axenic MHOM-ET-67/82	IC₅₀ = 20.4 ± 0.03 μg/ml
Central nervous system activities
Anti-depression and anxiolytic activity	In vitro	Madin-Darby canine kidney cell line	IC₅₀ = 2.31 ± 0.21 μM	Inhibition of OCT2	Li et al. (2016)
		Madin-Darby canine kidney cell line	IC₅₀ = 4.09 ± 1.2 μM	Inhibition of OCT3
		hOCT2-transfected cells	IC₅₀ = 0.120 μM	Decreased 5-HT and NE mediated by OCT2
		hOCT2-transfected cells	IC₅₀ = 0.819 μM	Decreased 5-HT and NE mediated by OCT2
		hOCT3-transfected cells	IC₅₀ = 0.278 μM	Decreased 5-HT and NE mediated by OCT3
		hOCT3-transfected cells	IC₅₀ = 0.184 μM	Decreased 5-HT and NE mediated by OCT3
		PMAT-transfected cells	IC₅₀ = 3.84 μM	Decreased 5-HT and reduce NE uptake mediated by PMAT
		PMAT-transfected cells	IC₅₀ = 2.99 μM	Decreased 5-HT and reduce NE uptake mediated by PMAT
	In vivo	Male ICR albino mice	5, 10, 20 mg/kg of i.p	Reduced the duration of immobility in mouse tail suspension test
	In vitro	Monoamine oxidase-A	IC₅₀ = 57.73 ± 5.26 μM	Inhibitory activity against MAO-A enzyme	Zhang et al. (2019)
	In vitro	MAO-A from rat brain mitochondria	IC₅₀ = 4 μM	Inhibitory activity against MAO-A enzyme	Kong et al. (2001)
Anti-Alzheimer’s disease	In vitro	Acetylcholinesterase	IC₅₀ = 0.57 μM	Inhibitory activity against AChE	Lin et al. (2020)
	In vitro	Recombinant human IDO-1	IC₅₀ = 206 μM	Inhibitory activity against IDO-1	Yu et al. (2010)
	In vitro	HEK 293-hIDO1 cells	IC₅₀ = 17.8 μM	Inhibitory activity against IDO-1	Yu et al. (2010)
	In vitro	HT22 cells	5, 10 μmol/L	Antioxidation and inhibition of the mitogen-activated protein kinases (MAPK) pathways	Jiang et al. (2015)
	In vitro	SH-SY5Y cells induced by Aβ 25-35	10 mM	Upregulation of miR-223-3p, inhibition of the HDAC4 expression, suppression of apoptosis and OS, and improved cell proliferation	Duan and Chen (2021)
	In vivo	APP/PS1 transgenic mice	5, 10 mg/kg	Decreased the levels of Aβ plaques in the cortex and hippocampus, alleviated the learning and memory deficits	Wang et al. (2019b)
	In vivo	C57BL/6 wild-type (WT) mice	High dose	Regulated the abundance of the microbiota and increased the amounts of beneficial bacteria	Wang et al. (2019b)
Neuroprotective effect	In vitro	H₂O₂-induced rat pheochromocytoma line PC12 injury	0.01–10.0 μM	Increased cell viability and activities of SOD, HO-1; decreased LDH, MDA and ROS; inhibited apoptosis by inhibiting caspase-3 activation	Luo et al. (2011)
Treatment of ischaemic stroke	In vitro	mouse brain endothelial cells	5, 10, 20 μM	Reduced t-BHP-induced apoptosis; decreased ROS, MDA and 4-HNE; improved MMP and eNOS; inhibit IL-1β, TNF-α and IL-6; prevented decreases in PPAR-γ	Wu et al. (2020)
Anti-parkinsonian	In vitro	MAO-B from rat brain mitochondria	IC₅₀ = 62 μM	Inhibitory activity against MAO-B enzyme	Kong et al. (2001)
Effects on bones
	In vivo	Titanium Particle-induced murine calvarial osteolytic model (C57BL/6 mice)	100 mg/kg	Increased BMD and BV/TV, reduced bone erosion and the number of osteoclasts	Li et al. (2018)
	In vitro	bone marrow-derived macrophages	5–20 µM	Inhibited RANKL-induced osteoclast formation and bone resorption by the suppression of MAPKs signaling pathways and downregulation of NFATc1, TRAP, CTR and CTSK	Li et al. (2018)
	In vivo	collagen-induced arthritis (CIA) rats	20 mg/kg; 50 mg/kg	Inhibited NF-κB and MAPKs stimulated by TNF-α and inhibited bone destruction	Qiu et al. (2018)
Other pharmacological activities
Effect on gastrointestinal tracts	In vitro	Gastrointestinal tract smooth muscles isolated from rat	100 μM	Increased the amplitude of contractile responses of jejunum and ileum longitudinal muscles, antrum circular muscles and smooth muscles in distal colon, and activated acetylcholine receptors	Yuan et al. (2011)
Effect on gastrointestinal tracts	In vivo	Male Wistar rats	0.1, 0.3 and 1 mg/kg	Offset of postoperative ileus-induced delayed gastric emptying and intestinal transit	Zhang et al. (2012)
Hepatoprotective activity	In vitro	t-BHP-injured rat hepatocyte BRL-3A cells	EC₅₀ = 15.7 ± 3.3 μM	Decreased the release of LDH	Wang et al. (2016)