Views: 1000 Author: Lin LIU Publish Time: 2025-09-28 Origin: Site
Berberine (also known as berberine hydrochloride), a typical member of the isoquinoline alkaloid family, has attracted significant attention in modern pharmacological research due to its diverse biological activities, including antibacterial, antioxidant, anti-inflammatory, and regulatory effects on glucose and lipid metabolism. In recent years, its multitarget intervention role in organ protection has become increasingly clear, providing a new perspective for the prevention and treatment of metabolic diseases and organ injury-related disorders. This article systematically reviews the protective mechanisms of berberine on the liver, stomach, kidneys, intestines, and pancreas, and conducts an academic popular science analysis combined with experimental evidence.
Regulation of Lipid Metabolism and Excretion: In a rat NAFLD model induced by a high-fat diet, berberine can increase the levels of total bile acids in the liver and feces. By upregulating the expression of key molecules such as hepatic cytochrome 7A1 (CYP7A1) and microsomal triglyceride transfer protein (MTTP), and downregulating the expression of liver X receptor α (LXRα), sterol regulatory element-binding protein (SREBP), Niemann-Pick C1-like 1 (NPC1L1), and fatty acid synthase (FAS), it inhibits fatty acid synthesis and the activity of the "intestinal-liver complex I", thereby dual-promoting fat metabolism and fecal lipid excretion.
Improvement of Hepatic Pathological Injury: By inhibiting macrophage infiltration, neutrophil activation, hepatic stellate cell activation, as well as reducing proinflammatory macrophage polarization and abnormal extracellular matrix deposition, berberine can significantly alleviate hepatic steatosis and organizational structure disorder in NAFLD model rats.
Activation of Energy Metabolism Pathways: In a high-fat diet mouse model, berberine can activate the hepatic AMPK/SIRT1 energy-sensing axis, promote PPARγ deacetylation and the expression of thermogenic proteins, drive adipose tissue remodeling, reasonable distribution, and improvement of thermogenic function, thereby indirectly reducing the metabolic burden on the liver.
Regulation of Intestinal Flora and Anti-Inflammation: In a genetically obese mouse model, berberine can increase the abundance of beneficial bacteria such as Bifidobacterium and Akkermansia muciniphila in the cecal contents, alleviating hypertriglyceridemia and systemic inflammation. For rats with hepatic ischemia-reperfusion injury, it can downregulate the expression of NLRP3 inflammasome-related proteins (NLRP3, ASC, Caspase-1) and reduce cell apoptosis.
Antagonism of Drug-Induced Hepatic Injury: Against hepatotoxicity induced by methotrexate, areca nut water extract, etc., berberine can reverse hepatic steatosis and dyslipidemia by downregulating the expression of p38-MAPK, NF-κB, Kelch-like ECH-associated protein 1 (Keap1), or reducing the expression of FAS and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR).
In addition, the combined use strategy of berberine can further enhance the therapeutic effect on NAFLD: the combination of berberine with Pinus guineensis and gardenia coffee can exert a synergistic effect by regulating miR-122, miR-34a, and the intestinal microbiome; the combination with sitagliptin can inhibit the p-ERK/ERK signal, increase the expression of adiponectin receptor 2 (AdipoR2), and promote adipose tissue remodeling in hyperlipidemic rats.
Alleviation of Hp-Induced Gastric Mucosal Epithelial Cell Injury: In vitro experiments have shown that medium and high doses of berberine can reverse the negative effects of Hp on human gastric mucosal epithelial GES-1 cells—restoring cell viability, inhibiting cell apoptosis, reducing the secretion of IL-1β/IL-8 and LDH activity, while regulating the protein levels of p-ERK1/2, Bax (pro-apoptotic), and Bcl-2 (anti-apoptotic). The combination of berberine with the ERK1/2 inhibitor PD98059 can further enhance the above protective effects, confirming that its mechanism is closely related to the regulation of the ERK1/2 signaling pathway.
Improvement of Pathological Status of Chronic Atrophic Gastritis: In a rat model of chronic atrophic gastritis, berberine can improve the pathological characteristics of gastric tissue, reduce gastrin levels, reduce inflammatory responses and abnormal proliferation by inhibiting inflammatory factors such as NF-κB, TNF-α, cyclooxygenase-2 (COX-2), IL-6α, IL-17a, and IFN-γ, and downregulating the activity of the TGF-β1/PI3K/Akt/mTOR/p70S6K signaling axis; at the same time, it promotes the expression of protein tyrosine phosphatase (SHP-1) and autophagy marker LC3II to maintain gastric mucosal homeostasis.
Protection of Renal Tubular Epithelial Cells: In a human renal cortical proximal tubular epithelial HK-2 cell injury model, berberine can reduce the production of mitochondrial reactive oxygen species (ROS), promote the expression of growth arrest-specific gene (GAS6), and at the same time upregulate the expression of E-cadherin and downregulate the expression of NLRP3/Caspase-1, thereby reducing Caspase-1 enzyme activity and IL-1β secretion and alleviating cell injury.
Alleviation of Drug/Pathology-Induced Kidney Injury: In a rat kidney injury model induced by adriamycin, it alleviates the change of tissue structure, reduces the levels of urea and creatinine by reducing the expression of TGF-β, Caspase-3, and NF-κB and alleviating oxidative stress; for renal ischemia-reperfusion injury, it can reduce serum chromium, blood urea nitrogen, and the contents of IL-1β/TNF-α in the kidneys by inhibiting the SIRT1/Nrf2 signaling pathway and the expression of NLRP3/Caspase-1; for renal injury in hyperuricemic mice induced by potassium oxonate and hypoxanthine, it can significantly reduce serum uric acid, urea nitrogen, and creatinine, and downregulate the activity of the NLRP3/Caspase-1/IL-1β pathway.
Inhibition of Renal Fibrosis: In a mouse model of non-metabolic classic renal fibrosis, berberine can downregulate the expression of renal α-smooth muscle actin (α-SMA, a fibrosis marker) and IL-1β, upregulate the expression of E-cadherin, and alleviate glomerular compensatory hypertrophy, peritubular space widening, and inflammatory cell infiltration. In addition, it can form a supramolecular self-assembly structure with aristolochic acid, block the metabolism of aristolochic acid, maintain the homeostasis of intestinal flora, and thus reduce the risk of acute kidney injury.
Inhibition of Pathogenic Bacteria and Regulation of Intestinal Flora: In vitro experiments have confirmed that berberine has a strong inhibitory effect on intestinal pathogenic bacteria such as Shigella dysenteriae, Shigella flexneri, Salmonella, and Staphylococcus aureus; in the IBS rat model, it can increase the proportion of Lactobacillaceae and decrease the proportion of Enterobacteriaceae in the intestine, improve abnormal defecation, visceral hypersensitivity, and intestinal microinflammation, confirming that flora regulation is one of the core mechanisms.
Improvement of Inflammation and Mucosal Barrier in Ulcerative Colitis: In a mouse model of UC induced by dextran sulfate sodium (DSS), a high dose of berberine can significantly reduce the disease activity index (DAI), colonic gross morphological damage index, and histological damage index. By downregulating TNF-α/IL-1β and upregulating IL-10 (an anti-inflammatory factor), and at the same time increasing the mRNA and protein expression of tight junction protein claudin-1, it maintains the structural stability of the intestinal mucosal junction complex, reduces intestinal wall permeability, and thus reduces the activation of local immune inflammatory responses. In addition, it can inhibit the abnormal expression of intestinal stem cell markers and the destruction of tight junction proteins, maintain the homeostasis of the intestinal mucosal mechanical barrier, and further alleviate colonic inflammation.
Alleviation of Intestinal Stress-Related Pain: For irritable bowel syndrome (visceral hypersensitivity), berberine can significantly increase the pain threshold, alleviate chronic visceral pain responses, and exert a significant analgesic effect, providing support for the comprehensive intervention of intestinal dysfunction.
In a mouse model of severe acute pancreatitis, the protective effect of berberine focuses on "anti-inflammation, anti-oxidation, and inhibition of NF-κB activity": compared with the model group, the pancreatic mass index of mice in the administration group was significantly reduced; the serum levels of IL-6, TNF-α (pro-inflammatory factors), MDA (oxidative stress marker), MPO (myeloperoxidase, an indicator of inflammatory infiltration), amylase, and lipase were significantly decreased, while the levels of HO-1 (heme oxygenase-1, an antioxidant enzyme) and IL-10 (anti-inflammatory factor) were significantly increased; the mRNA expressions of TNF-α and IL-6 in pancreatic tissue were significantly downregulated, while the mRNA expressions of IL-10 and HO-1 were significantly upregulated; the protein expressions of HO-1, IκB-α, and NF-κBp65 were significantly decreased, and the positive cell rate of NF-κBp65 was significantly reduced. The above results confirm that berberine can alleviate pancreatic inflammatory injury and oxidative stress injury by activating HO-1 activity, and its mechanism may be related to the inhibition of NF-κB activity.
As a naturally derived multitarget drug, berberine exhibits clear protective effects on multiple organs such as the liver, stomach, kidneys, intestines, and pancreas by regulating metabolic pathways (e.g., AMPK/SIRT1, TGF-β/PI3K), inflammatory signals (e.g., NF-κB, NLRP3), apoptosis-related molecules (e.g., Bax/Bcl-2), and intestinal flora. Its advantages lie in its broad mechanism of action, high safety from natural sources, and the fact that combination strategies can further expand the efficacy boundary. In the future, with the in-depth analysis of its molecular targets, optimization of dosage forms (e.g., improving bioavailability), and advancement of clinical research, berberine is expected to play a more important clinical role in the prevention and treatment of organ injury-related diseases, providing a new research direction for the field of "natural drugs-organ protection".
[2] Chen, M. L., Li, Z. Q., Fan, Q. Q., et al. (2022). Research Progress on Pharmacological Effects and Related Mechanisms of Berberine. Chinese Traditional and Herbal Drugs, 53(18), 5861-5872.
Important Reminder：All content in this article is for general reference only and is provided solely to offer information support for practitioners in the nutrition and health industry. Descriptions related to efficacy are supported by corresponding data, but they do not represent claims or guidance for consumers. Content related to health, medical care, and technological applications is for reference only. For medical matters, please consult professional medical institutions and follow medical advice. This article does not provide any medical recommendations.
