Berberine, also known as Coptidis Rhizoma, is a prevalent isoquinoline alkaloid celebrated for its multifaceted pharmacological activities, including antibacterial, antioxidant, anti - inflammatory, hypoglycemic, lipid - lowering, and anti - apoptotic properties. In recent years, with the continuous advancement of research, as a multi - targeted therapeutic agent, berberine has demonstrated remarkable protective effects on various organs. This review comprehensively summarizes the protective effects and underlying mechanisms of berberine on major organs, such as the liver, stomach, kidney, intestine, and pancreas. By regulating metabolic pathways, modulating inflammatory responses, and protecting cellular functions, berberine plays a crucial role in preventing and treating organ - related diseases, offering new perspectives for clinical applications and drug development.
Unveiling the Organ - Protective Powers of Berberine: A Comprehensive Review of Mechanisms and Advances
Berberine, a well - known natural isoquinoline alkaloid, has long been a subject of fascination in the field of modern pharmacology. From traditional herbal medicine to cutting - edge scientific research, this compound has continuously revealed its extraordinary potential. With a wide spectrum of biological activities ranging from antibacterial and antioxidant effects to anti - inflammatory and anti - apoptotic properties, berberine has emerged as a promising multi - targeted therapeutic agent. In recent years, an increasing number of studies have focused on its protective effects on various organs, uncovering new insights into its mechanisms of action and potential clinical applications.
Protective Effects and Mechanisms of Berberine on the Liver
Nonalcoholic fatty liver disease (NAFLD) is a pathological condition closely associated with metabolic syndrome. Berberine exerts its hepatoprotective effects through multiple regulatory mechanisms. Clinically, it has been shown to reduce triglyceride levels, serum total cholesterol (TC), and insulin resistance (IR) in NAFLD patients, effectively improving related symptoms by modulating glucose and lipid metabolism.
In rat models of NAFLD induced by high - fat diets, berberine promotes fat metabolism and fecal lipid excretion. It achieves this by increasing the levels of total bile acids in the liver and feces, upregulating the expression of cytochrome P450 7A1 and microsomal triglyceride transfer protein, while downregulating the levels of liver X receptor α, sterol regulatory element - binding protein, intracellular cholesterol transporter 1, fatty acid synthase (FAS), stearoyl - CoA desaturase 1, fatty acid - binding protein 1, and carnitine palmitoyltransferase 1A. Additionally, berberine inhibits fatty acid synthesis and the gut - liver axis complex I. It also improves steatosis and structural lesions by suppressing macrophage infiltration, activation of neutrophils and hepatic stellate cells, polarization of pro - inflammatory macrophages, and abnormal deposition of the extracellular matrix.
Furthermore, research has demonstrated that berberine activates the AMPK/SIRT1 axis, an energy metabolism - sensing pathway in the liver of high - fat - diet mice. By increasing the deacetylation of PPARγ and the expression of thermogenic proteins, it promotes adipose tissue remodeling, distribution, and thermogenesis. In genetically obese mouse models, berberine increases the content of Bifidobacterium and Akkermansia muciniphila in the cecal contents, alleviating hypertriglyceridemia and inflammatory responses. In a rat model of liver ischemia - reperfusion injury, berberine reduces the expression of NLRP3, apoptosis - associated speck - like protein containing a CARD, and Caspase - 1, thereby mitigating cell apoptosis. In non - alcoholic steatohepatitis models, berberine significantly improves the levels of pro - inflammatory cytokines and free fatty acids, reduces the expression of chemerin, chemokine - like receptor 1, and C - C motif chemokine receptor 2 in the liver, and restores the ratio of regulatory T cells to T helper 17 cells.
Berberine also shows antagonistic effects against drug - induced liver injury. For example, it downregulates the expression of p38 - mitogen - activated protein kinase (MAPK), NF - κB, and Kelch - like ECH - associated protein 1, effectively reducing the hepatotoxicity of methotrexate. It can also reverse liver steatosis and dyslipidemia induced by areca nut water extract by decreasing the expression of fatty acid synthase and 3 - hydroxy - 3 - methylglutaryl - CoA reductase.
Protective Effects and Mechanisms of Berberine on the Stomach
Studies have found that berberine can alleviate the damage of human gastric mucosal epithelial cells induced by Helicobacter pylori (Hp). Medium and high doses of berberine can reverse the effects of Hp on the viability, apoptosis, secretion of IL - 1β and IL - 8, LDH activity, and the protein levels of p - ERK1/2, Bax, and Bcl - 2 in GES - 1 cells. Compared with the high - dose berberine group, the combination of the extracellular signal - regulated kinase (ERK1/2) inhibitor PD98059 and berberine can further reverse the effects of Hp on these indicators in GES - 1 cells, indicating that berberine reduces Hp - induced damage to GES - 1 cells through anti - inflammatory, cell - viability - enhancing, and anti - apoptotic effects.
In rats with chronic atrophic gastritis, berberine improves the pathological characteristics of gastric tissues, reduces gastrin levels, and inhibits the expression of inflammatory factors such as NF - κB, TNF - α, cyclooxygenase - 2, IL - 6α, IL - 17a, interferon - γ, and TGF - β1 - axis - related signals including TGF - β1, PI3K, p - Akt/Akt, p - mTOR/mTOR, and p70 ribosomal protein S6 kinase. It also promotes the expression of protein - tyrosine phosphatase and LC3II.
Protective Effects and Mechanisms of Berberine on the Kidney
Berberine has also exhibited significant protective effects in kidney injury models. Research shows that berberine reduces the production of mitochondrial reactive oxygen species in the human renal proximal tubule epithelial HK - 2 cell injury model and promotes the expression of growth arrest - specific genes. It upregulates the expression of E - cadherin, downregulates the expression of NLRP3 and Caspase - 1 proteins, and reduces the activity of Caspase - 1 enzyme and the secretion of IL - 1β, thereby protecting HK - 2 cells from injury.
In a rat model of kidney injury induced by adriamycin, berberine alleviates structural changes by reducing the expression of transforming growth factor - β (TGF - β), Caspase - 3, and NF - κB and decreasing oxidative stress. It also reduces the levels of urea and creatinine, exerting a protective effect on the kidneys. Moreover, in a model of renal ischemia - reperfusion injury, berberine protects the kidneys by decreasing the concentrations of serum chromium and blood urea nitrogen, reducing the levels of IL - 1β and TNF - α in the kidneys, and inhibiting the SIRT1/nuclear factor E2 - related factor 2 (Nrf2) signaling pathway and the expression of related Caspase - 1 and NLRP3 in renal tissues.
In a mouse model of hyperuricemia induced by potassium oxonate and hypoxanthine, berberine protects the kidneys by significantly reducing serum uric acid, blood urea nitrogen, and creatinine levels and downregulating the expression of NLRP3, Caspase - 1, and IL - 1β. In a non - metabolic classic renal fibrosis model, berberine alleviates symptoms such as compensatory hypertrophy of some glomeruli, widened peritubular spaces, and inflammatory cell infiltration in mice by inhibiting the expression of α - smooth muscle actin and IL - 1β proteins in the kidneys and increasing the expression of E - cadherin.
Additionally, it has been found that berberine and aristolochic acid form a supramolecular self - assembly structure, which blocks the metabolism of aristolochic acid, protects the homeostasis of the gut microbiota, and significantly reduces the acute renal injury caused by aristolochic acid.
Protective Effects and Mechanisms of Berberine on the Intestine
The mechanism of berberine in treating gastrointestinal infections is related to its ability to inhibit the growth of pathogenic intestinal bacteria, improve the balance of the gut microbiota, and protect the function of the gastrointestinal mucosa. Berberine has a strong inhibitory effect on Shigella dysenteriae, Shigella flexneri, Salmonella, and Staphylococcus aureus in the gut microbiota.
Studies on the effect of berberine on the gut microbiota of rats with irritable bowel syndrome (IBS) have shown that after berberine intervention, the increased defecation, visceral hypersensitivity, and intestinal micro - inflammation in IBS rats are significantly improved. The mechanism may be related to the increase in the proportion of Lactobacillaceae bacteria and the decrease in the proportion of Enterobacteriaceae bacteria in the intestines of IBS rats. Berberine also significantly inhibits the growth of pathogenic bacteria Enterobacter and Enterococcus while promoting the growth of beneficial bacteria Lactobacillus and Bifidobacterium.
In a mouse model of ulcerative colitis (UC) established by dextran sulfate sodium, the clinical manifestations and histopathological features of colitis in mice in each treatment group were improved to varying degrees. The high - dose berberine group showed significant decreases in the disease activity index, macroscopic colonic damage index, and colonic tissue damage index scores. After berberine treatment, the levels of TNF - α and IL - 1β in the colonic tissues of mice were significantly reduced, while the levels of IL - 10, claudin - 1 mRNA, and protein expression were increased compared with the model group.
Berberine effectively treats colonic inflammation in UC mice by increasing the expression levels of the tight - junction protein claudin - 1 at both the protein and mRNA levels, maintaining the structure and function stability of the junction complex to a certain extent, reducing intestinal wall permeability, and thus decreasing the activation of local intestinal immune inflammatory responses and alleviating tissue damage. In addition, berberine inhibits colonic inflammation in UC mice by preventing the destruction of intestinal stem cell markers and tight - junction proteins, maintaining the homeostasis of the intestinal mucosal mechanical barrier, and plays a protective role in the occurrence and development of UC. When treating intestinal stress syndrome (visceral allergic reaction), berberine significantly increases the pain threshold, reduces chronic visceral pain responses, and exerts a significant analgesic effect.