Table 6.

Main clinical application and mechanism of berberine

Clinical application	Mechanism	Literature
Anti-diarrheal	Antibacterial (e.g., Vibrio cholerae) Inhibition of intestinal smooth muscle movement regulates intestinal motility Inhibition of intestinal mucosa K+’s influx restores intestinal barrier function	[10, 41–44]
Anticancer (cancer arising from leucocytes, liver, lung, stomach, colon, skin, oral, etc.)	Chemical carcinogenic protection Independent of the mevalonate pathway Directly induces apoptosis Downregulation of nuclear transcription factors Exertion of indirect effects Suppression of DNA	[45–54]
Anti-diabetic	Stimulation of AMPK activity and might inhibit PPARγ activity Promotion of the proliferation of 3T3-L1 pre-adipocytes, reduced lipid accumulation, and inhibition of their differentiation Insulinotropic effects Good action for lipid metabolism Targeting of non-coding RNAs Promotion the expression of GLUT1 Modulation of the gut microbiota	[55–61]
Anti-cardiovascular (e.g., Atherosclerosis)	Inhibition of the expression of LOX-1 through ET-1 receptors Impacts on potassium ion channels (K +) Increased NO and cGMP content Blockage of K + channels sensitive to ATP and voltage Inhibition of mitogen-activated kinase/extracellular signals	[62–65]
Anti-inflammatory and immune regulation (e.g., ulcerative colitis)	Inhibit cox-2, AP-1 binding Downregulation of activation of ERK 1/2 and p38 signallings pathways, Inhibition of the production of pro-inflammatory factors Downregulation of p-ERK, p-p38, and p-JNK activation Inhibition of the expression of monocyte chemoattractant protein 1 and cytokine-induced neutrophil chemoattractant 1 induced by lipopolysaccharide Inhibition of RNA virus reverse transcriptase activity Inhibition of the synthesis of anti-SRBC antibodies Reduced content of PGF2a in inflammatory tissues	[66–72]
Antipsychotic (e.g., depression, Alzheimer’s,)	Increased NE and 5-HT concentrations in the brain Promotion of axon extension and axon regeneration in PNS-damaged nerves Increased expression of BDNF mRNA in the hippocampus Actions on the pathological process of amyloid Aβ, inhibitings glial proliferation Inhibition of tau hyperphosphorylation induced by calmodulin A and its induced cytotoxicity Inhibition of MAO activity	[73–78]