Table 1 Pharmacological actions and therapeutic or regulatory mechanisms of HLJDD

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]