Table 1.

The metabolism and biological effects of AC in different models.

Category	Models	Biological effects	Ref.
Metabolism	Rats	The bioavailability is 0.12 %. Cmax can be 0.13 μg/mL (oral, 100 mg/kg) or 48.6 μg/mL (intravenous, 3 mg/kg).	[5]
	Beagle dogs	The absolute bioavailability is about 4 %. Cmax is 0.42 μg/mL (oral, 10 mg/kg).	[24]
	CKD rats	Cmax is 0.31 μg/mL.	[25]
	DN rats	Cmax can be 69.08 μg/L or 70.53 μg/L.	[26]
	Caco-2, HT-29	The total accumulation efficiency is about 0.10 %.	[27], [28]
Anti- inflammation	RBL-2H3	Inhibits the activity of cPLA2 with a Ki value of 5.9 μM.	[15]
	Raw264.7	Inhibits iNOS/NO expression by attenuating AP-1activation.	[39]
	RAW 264.7, THP-1	Inhibits free fatty acid-induced COX-2/PGE2 expression.	[40]
	A549	Decreases NF-κB, IL-1β, IL-6, IL-8, and caspase-3/-8/-9, increases NRF2, HO-1, NQO-1, and GCLC.	[42]
	U937	Induces SHP-1 phosphorylation, attenuates the activation of TAK1/JNK/AP-1, and decreases COX and NOS expression.	[44]
	Dendritic cells	Increases IL-10 expression by activating AhR expression.	[46]
	KU812	Suppresses MAPK/JNK signaling and inhibits CCL1–4, FCER1A, and NFATC1 expression.	[48]
	HMC-1	Decreases STAT5/6, IL-6, IL-13, TNFα, and IL-1β expression, down regulates MDM2, and up regulates p53.	[50]
	TRPV3- HEK293	Selectively inhibits 2-APB-activated human TRPV3 channel with an IC50 value of 14.1 μM.	[53]
Anti-oxidative stress	SY5Y	Protects against Aβ-induced ROS generation and mitochondrial dysfunctions and apoptosis.	[57]
	Rats	Alleviates I/R-induced increased production of SOD, GSH-Px, TAS, and TT and decreased levels of TOS, OSI, and MDA.	[59]
	Sheep oocytes	Reduces ROS production and lipid peroxidation and protects mitochondrial functions.	[64]
Anti-cancers	B16F10	Attenuates tyrosinase activity and inhibit melanin biosynthesis by activating ERK signaling and down regulating the expression of MITF, tyrosinase, and TRP-1.	[69]
	4T1	Inhibits the proliferative activity (IC50 = 117 μM).	[71]
	GBM cells	Inhibits metastasis and promotes cell apoptosis and autophagy by let-7 g-5p/HMGA2/Wnt/β-catenin signaling.	[73]
	Caco-2, HCT-116	Induces G1 cell cycle arrest and increases cell apoptosis by PI3K/AKT signaling.	[78]
	Du-145, PC-3	Decreases HMGB1/RAGE/TGFβI/II/Smad2/3, inhibits EMT.	[79]
	Mouse	Inhibits metastasis by decreasing NF-κB/MMP-2 signaling and promotes cell apoptosis by Bcl-2/Bcl-XL.	[82]
	JHH-7	Increases p53 expression and decreases KLK-1, -2, -4, -9, and -10 expression.	[84]
Neuro-protection	Mice	Protects against I/R-induced expression of HIF-1α, NF-κB, and VEGF.	[94]
	Rats	Decreases Aβ 1–40 production, inhibits Aβ 1–42 oligomerization	[96]
	PC12	Activates NRF2/HO-1 signaling, protects neuron against Aβ-induced injury.	[98]
	BV-2	Acts as an inhibitor of NF-κB and an agonist of AMPK.	[99]
	Rats	Increases Glut1, Glut3, and Glut4 expression, reduces ROS production, and protects against ICV-STZ-induced learning and cognitive impairment.	[102]
	Zebrafish	Protects against 6-OHDA-induced movement disorders and dopaminergic neuron death.	[105]
	RGC-5	Protects against H2O2-induced injury by mediating CASC2/miR-155/mTOR signaling.	[110]
Cardio-vascular protection	Rat serum	Inhibits ACE activity with an IC50 value of 365 μM.	[113]
	H9c2	Increases mitochondrial biogenesis, inhibits apoptosis.	[115]
	Rats	Improves the lipid profiles and the organ coefficients by AMPK/mTOR signaling.	[118]
Anti-diabetes	Caco-2	Inhibits SGLT1-mediated glucose absorption.	[120]
	βtc3 cells	Increases insulin biosynthesis and secretion by inhibiting oxidative stress and ERS.	[121]
Bone and cartilage protection	Rats	Inhibits MMP-13, MMP-3, and MMP-1 expression by decreasing MAPK/NF-κB signaling.	[19]
	Mice	Reduces osteoclastogenesis by attenuation of NF-κB pathway and stimulation of PI3K/AKT pathway.	[125]
	MC3T3-E1	Enhances proliferation and differentiation by increasing IGF-1/BMP/PI3K/mTOR signaling	[127]