Table 1.

Pharmacological actions and therapeutic or regulatory mechanisms of HLJDD

Pharmacological actions	Model	Mechanisms	Refs.
Anti-tumor	Hepatocellular carcinoma xenograft murine	Suppressing xenografted growth by inactivating eEF2 through the activation of AMPK signaling	[6]
	Hepatocellular carcinoma xenograft Hep G2 PLC/PRF/5	Inducing apoptosis Blocking cell cycle progression by regulating cell-cycle-related factor (p21/WAF1, cyclin B1, cyclin A, Cdc25C, and Cdc2) Promoting programmed cell death by modulating Bcl-2 Triggering mitochondrial pathway through membrane depolarization and caspase-9 activation Inhibiting NF-κB survival signaling pathway	[100]
Hepatoprotection	Thioacetamide	Restoring redox system, gut flora, and urea cycle	[24]
	Bile duct ligation	Restoring redox system, gut flora, Kreb’s cycle, and oxidation of branchedchain amino acids	[24]
	Bile duct ligation	Ameliorating energy metabolism, amino acid metabolism and gut microbiota metabolism Protecting oxidative injury	[25]
Anti-inflammatory	Carrageenan-induced rat air pouch A23187-stimulated peritoneal macrophages LPS-stimulated RAW 264.7 macrophages	Inhibiting inflammatory responses and eicosanoids generation from different lipoxygenases	[106]
	Carrageenan-induced mice paw edema LPS-stimulated RAW 264.7 macrophages	Reducing oxidative injury	[44]
	Collagen-induced arthritis rats	Regulating fatty acid oxidation and arachidonic acid metabolism	[19]
	LPS-stimulated RAW 264.7 macrophages	Suppressing the production of inflammatory mediators via inactivation of NF-κB and MAPKs, and degradation of IκBα	[108]
	Cecal ligation and puncture-induced septic model rats	Enhancing cholinergic anti-inflammatory pathway Inhibiting HMGB-1/TLR4/NF-κB signaling pathway	[4]
	Cecal ligation and puncture-induced septic model rats	Suppressing the production of proinflammatory cytokines Reversing the shift from Th1 to Th2 response and promote Th1/Th2 balance toward Th1 predominance Iinhibiting Th17 activation	[112]
	2,4-dinitrochlorobenzene-induced atopic dermatitis mice LPS-stimulated RAW 264.7 macrophages	Inhibiting MAPKs/NF-κB pathway	[115]
	LPS-induced gingivitis rats	Inhibiting AMPK and ERK1/2 pathway	[116]
	LPS-induced acute kidney injury mice	Inhibiting NF-κB and MAPK activation Activating Akt/HO-1 pathway Ameliorating disturbances in oxidative stress and energy metabolism	[26]
Anti-allergy	Antigen-induced RBL-2H3 cells	Suppressing allergic mediators via inactivation of MAPKs and Lyn pathway	[108]
Modulation of blood lipid	ApoE(-/-) mice Primary bone marrow-derived macrophage Foam cells	Regulating the functional differentiation of monocytes, macrophages, and foam cells	[119]
	High-fat diet-induced hyperlipidemia rats	Activating the activityof lipid metabolism enzyme Enhancing the expressions of LDLR and PPAR γ mRNAs	[14]
	High-fat diet and streptozotocin-induced T2DM rats	Inhibiting the activity of intestinal pancreatic lipase	[30]
Modulation of blood glucose	streptozotocin-induced T2DM rats	Enhancing GLP-1 secretion in gut to promoting insulin secretion and improving function of β cell	[120]
	Min6 cells NCI-H716 cells	Elevating intracellular cAMP levels to promote GLP-1 secretion and insulin secretion Increasing β cell mass through hyperplasia and hypertrophy	[121]
Central nervous system diseases	MCAO rats	Inhibiting neuron apoptosis and enhancing its proliferation through activating PI3K/Akt signaling pathway and HIF-1α	[28]
	MCAO rats	Inducing protective autophagy through the regulation of MAPK signals	[126]
	MCAO rats	Ameliorating the disordered metabolisms in energy, membrane and mitochondrial, amino acid and neurotransmitter Alleviating the inflammatory damage and the oxidative stress from ROS Recovering the destructed osmoregulation	[127]
	SAMP8	Modulating gene expressions in signal transduction (Dusp12, Rps6ka1, Rab26, Penk1, Nope, Leng8, Syde1, Phb, Def8, Ihpk1, Tac2, Pik3c2a), protein metabolism (Ttc3, Amfr, Prr6, Ube2d2), cell growth and development (Ngrn, Anln, Dip3b, Acrbp), nucleic acid metabolism (Fhit, Itm2c, Cstf2t, Ddx3x, Ercc5, Pcgfr6), energy metabolism (Stub1, Uqcr, Nsf), immune response (C1qb), regulation of transcription (D1ertd161e, Gcn5l2, Ssu72), transporter (Slc17a7, mt-Co1), nervous system development (Trim3), and neurogila cell differentiation (Tspan2)	[132]
	APPswe/PS1dE9 mice	Ameliorating neuroinflammation and sphingolipid metabolic disorder	[34]
	HEK 293 cells	Inhibiting indoleamine 2,3-dioxygenase activity	[133]
Anti-infection	Candida albicans	Inhibiting formation of hyphae and colony morphologies through downregulating the expression of HWP1, ALS3, UME6 and CSH1	[136]
	Pseudomonas aeruginosa	Reducing pyocyanin pigment, elastolytic activity, proteolytic activity, biofilm formation, and bacterial motility	[137]
	H1N1	Inhibiting NA activity	[139]
Modulation of microbiota	High-fat diet and streptozotocin-induced T2DM rats	Ameliorating hyperglycemia and restoring the disturbed gut microbiota structure and function through increasing short chain fatty acids-producing bacteria while reducing conditioned pathogenic bacteria	[143]