Table 1.
Effects of RC and its bioactive compounds on T2DM complications.
| Diabetic complications | Drug/ extract |
Model | Dose and treat time | Described effects | Anti-diabetic mechanism | Ref |
|---|---|---|---|---|---|---|
| Diabetic vascular dysfunction | BBR | Wistar rats, STZ + high-fat diet (HFD) | 100 mg/kg/day, 8w | FBG and TG levels↓; endothelium-dependent vasorelaxation impaired in aorta↓ | eNOS mRNA and protein↑ and NOX4 protein expressions↓ in aortas | (Wang et al., 2009a) |
| BBR | SD rats, STZ + HFD; human artery endothelial cells, high glucose+palmitate | 200 mg/kg/day, 4 weeks; 2.5–10 µmol/L | Insulin-induced vasodilatation↑; cell viability and autophagy↑ | Phosphorylation of the insulin receptor and its downstream AMPK, Akt, eNOS↑; down-regulating insulin receptors attenuated BBR-induced p-AMPK. | (Geng et al., 2016) | |
| BBR | Human umbilical vein endothelial cells, 30 mM glucose | 25 µM, 60 min | Endothelium-dependent vasodilatations↑ | Interaction between eNOS and HSP90↑; NO production↑; NO release by berberine is eNOS and AMPK-dependent; phosphorylation of the a-catalytic subunit of AMPK at its activation site (Thr172)↑; cGMP levels in the isolated rat aorta↑ | (Wang et al., 2009b) | |
| BBR | Human umbilical vein endothelial cells, palmitate | 1.25, 2.5, and 5 µmol/L, 24 h | NO levels↑; production of ROS↓; NOX4 protein expression↓; expression of eNOS↑; protein expressions of AMPK and p-AMPK↑ | (Zhang et al., 2013) | ||
| BBR | SD rat, STZ + HFD; cerebral vascular smooth muscle cells, 20 mM D-glucose | 100 and 200 mg/kg/day, 8 weeks; 10 µM, acute extracellular application |
Blood glucose↓; systolic and diastolic blood pressure↓; relaxation in the presence of 20 mM D-glucose↑ | Large-conductance Ca2+-activated K+ channel and expression of β1-subunit at protein or mRNA levels↑ | (Ma et al., 2017) | |
| BBR | Microvascular endothelial cells, hypoxic/high‐glucose | 30 µM, 24 h | Proliferation and migration↑ | DPP-4 expression↓; expressions of VEGF, eNOS, HIF-1α, and SIRT1↑ | (Mi et al., 2018) | |
| Diabetic heart disease | BBR | SD rat, STZ + HFD | 200 mg/kg/day, 4 weeks | Cardiac fibrosis and dysfunction↓ | IGF-1R expression in cardiac fibroblasts↓; MMP-2/MMP-9, α-SMA, and collagen I expressions in diabetic hearts↓ | (Li et al., 2018a) |
| BBR | SD rat, STZ | 100 and 150 mg/kg/day, 12 weeks | FBG↓, left ventricular systolic pressure and left ventricular end diastolic pressure absolute value↓; heart mass index and degree of cardiac fibrosis↓ | Expressions of TGF-β1, CTGF, collagen 1 and collagen 3↓ | (Lu et al., 2016) | |
| BBR | Rat primary cardiomyocyte, high glucose and insulin | 1, 3, and 10 µM, 48 h | Cardiomyocyte hypertrophy↓ | Expressions of PPARα, eNOS, and NO↑; activation of PPARα could directly modulate the expression of eNOS. | (Wang et al., 2013b) | |
| BBR | Wistar rats, STZ + HFD; H9c2 cells, palmitate | 100 mg/kg/day, 16 weeks; 10 µM, 48 h | Systolic and diastolic dysfunction↓; fasting blood insulin↑, FBG, TC, and TG levels↓; cardiac collagen deposition↓ | Cardiac TGF-β expression↓; pAMPK/AMPK, pAKT/AKT, and pGSK3β/GSK3β↑; α-myosin heavy chain (α-MHC) expression↑; β-MHC expression↓ | (Chang et al., 2015) | |
| BBR | SD rat, STZ + ischemia/reperfusion | 10 mg/kg/day (i.p.), 6 weeks | Blood glucose↓; body weight↑; recovered the hemodynamic parameters | Protein expression of Kir6.2 subunits in the diabetic hearts↑ | (Kaya et al., 2018) | |
| BBR | Wistar rats, STZ + HFD + ischemia/reperfusion | 100 mg/kg/day, 7 days | Ischemia-reperfusion injury infarct size and arrhythmia↓; serum TG, TC, and MDA levels↓ | AMPK activity in nonischemic areas↑; AKT↑, GSK3β↓, ratio of AMP/ATP↑, and adenosine diphosphate to ATP↑in nonischemic areas | (Chang et al., 2016) | |
| BBR | Wistar rats, isoproterenol+STZ | 100 mg/kg/day, 30 days | Blood glucose↓; body weight↑; liver, kidney, and islets damage↓; TC, TG, and LD↓; HDL↑ | HbA1c (hemoglobin a1c) and isoenzyme of creatine phosphokinase (CPK-MB) levels↓; creatinine (Cr) and ALT levels ↓ | (Suman et al., 2016) | |
| BBR | SD rats, STZ+ ischemia | 100 mg/kg/day, 7 days | Arrhythmia↓; QTc interval↓; diminished I(to) and I(Ca) current densities↑ | Decreased Ito in ischemic hearts was associated with the expression of Kv4.2 | (Wang et al., 2012) | |
| BBR | SD rat, STZ + HFD+ coronary artery occlusion | 180 mg/kg/day, 14 days | Recovering resting membrane potential; I(K1) current and current density↑; electrophysiological disturbance↓, | Expression of I(Kir2.1)↑ | (Wang et al., 2011) | |
| BBR | SD rats, STZ + HFD+ ischemia/reperfusion; neonatal rat | 100, 200, and 400 mg/kg/day, 4 weeks | Cardiac systolic/diastolic function↑; myocardial apoptosis↓in diabetic rats; hypoxia/reoxygenation-induced myocardial apoptosis↓ | Bcl-2/Bax ratio↑; caspase-3 expression↓; activation of PI3K-Akt↑; AMPK and eNOS phosphorylation↑ | (Chen et al., 2014) | |
| Diabetic hyperlipidemia | RC extract | SD rat, STZ + HFD | 7.88 g/kg/day, 30 days | Blood lipid level↓; insulin resistance↓ | The expressions of SREBP-1c and SCAP in liver↓ | (Liu et al., 2018) |
| Polysaccharides | ICR mice, STZ + HFD | 25, 50, and 100 mg/kg/day, 28 days | FBG, TG, and TC↓; | SOD and CAT activities in pancreas↑; MDA content in pancreas↓ | (Jiang et al., 2013) | |
| Polysaccharides | Wistar rats, STZ + HFD | 20, 50, and 100 mg/kg/day, 28 days | FBG, TG, TC↓ | GSH-Px, SOD, and CAT activities↑; GSH and MDA contents↓; JNK and phospho-IRS1 expression↓; expression of phospho-PI3Kp85 and GLUT-4↑ | (Jiang et al., 2015a) | |
| Pal, Jat | KK-Ay mice; HepG2 cells | 225 mg/kg/day, 40 days; 5 mg/ml, 24 h |
Food and water intake↓; TC and TG↓; HDL-C↑ | (Ma et al., 2016a) | ||
| Jat | Obesity mice | 20 and 100 mg/kg/day, 8 weeks | Liver-to-body weight ratio and pathological alterations of liver↓; serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), TG, TC and LDL-C levels↓, glucose tolerance, and insulin sensitivity↑ | Hepatic mRNA levels of SREBP-1c and FAS↓; PPAR-α and CPT1A mRNA expressions↑ | (Yang et al., 2016a) | |
| Col | Syrian golden hamsters, high fat and cholesterol diet | 23.35, 46.7, 70.05 mg/kg/day, 33 days | TC, TG, and LDL-C↓; HDL-C↑; conversion of cholesterol to bile acids↑ | CYP7A1 activation↑; mRNA and protein expressions of FTF, HNF-4α↑ | (Wang et al., 2016b) | |
| Brb | HepG2 cells | 15 µm, 24 h | Intracellular cholesterol contents↓ | Hepatic PCSK9↓ and LDLR↑ via the ERK1/2 signal pathway | (Cao et al., 2018b) | |
| BBR | KK-Ay mice | 225 mg/kg/day, 40 days | Serum HDL-C↑ | (Ma et al., 2016a) | ||
| BBR | Golden hamster, HFD | 50 and 100 mg/kg/day, 6 weeks | Plasma TC, TG, LDL-C, and FFA content↓; plasma MDA and ApoB level↓; SOD level↑ | mRNA expression of skeletal muscle GLUT4↑; liver LDLR mRNA expression↓ | (Liu et al., 2015) | |
| BBR | Wistar rats, STZ + HFD; 3T3-L1 cells; | 150 and 300 mg/kg/day, 16w; 4 µM, 8 days | Lipid accumulation↓ | PPARα/δ/γ, CDK9 and cyclin T1 mRNA and protein expressions in adipose tissue↑; lipoprotein lipase(LPL) activity↑; activating protein 2 (aP2), TNF-α, and FFA↓ | (Zhou and Zhou, 2010) | |
| Diabetic nephropathy | BBR | SD rat, STZ | 100 and 200 mg/kg/day, 8 weeks | FBG↓; BUN, urinary total protein (UTP), and Cr↓; ECM and renal fibrosis↓ | Ratio of MMP2/TIMP2 and MMP9/TIMP1↑; TGFβ1, FN, and collagen IV expressions↓ | (Ni et al., 2015) |
| BBR | SD rat, STZ; mesangial cells, high glucose | 200 mg/kg/day, 12 weeks; 10, 30, and 90 µM, 24 h | Restored metabolic parameters and renal morphology; MDA level↓; SOD activity↑ | RhoA-GTP and its substrate p-MYPT↓; levels of IκBα↑; NF-κBp65↓; intercellular adhesion molecule-1(ICAM-1)↓; TGF-β1 and FN overproduction↓; ROS generation↓ | (Xie et al., 2013) | |
| BBR | SD rat, STZ; primary glomerular mesangial cells, high glucose | 200 mg/kg/day, 12 weeks | Typical symptoms (more eating, drinking, urine, less body weight)↓; FBG, BUN, Cr, 24h albuminuria, and kidney weight/body weight ratio↓ | mRNA and protein expressions of S1P2 receptor↓; S1P2 receptor mediated FN expression↓; SphK1 activity and S1P production↓; NF-κBp65 nuclear translocation↓; NF-κB specific inhibitor obviously decreased the expression of S1P2 | (Huang et al., 2012) | |
| BBR | C57BL/6 mice, alloxan | 300 mg/kg/day, 12 weeks | FBG, kidney/body weight ratio, BUN, serum creatinine and 24h albuminuria↓; renal hypertrophy↓ | TGF-β1 synthesis, FN, and Col IV accumulation↓; SphK1 expression and S1P production↓ | (Lan et al., 2010) | |
| BBR | Mesangial cells, high glucose | 10, 30, and 90 µM, 48 h | Activity and expression of SphK1↓; expressions of α-SMA, FN, TGF-β1, and AP-1↓; SphK1 was regulated by AP-1 | (Lan et al., 2012) | ||
| BBR | SD rat, STZ + HFD; mesangial cells, high glucose | 10, 50, and 200 mg/kg/day, 4 weeks; 30, 60, and 90 µM, 24 h | FBG and body weight↓; the majority of biochemical and renal function parameters and histopathological changes↓ | Production of AGEs↓ induced levels of RAGE, P-PKC-β, and TGF-β1 in injured kidneys↓ | (Qiu et al., 2017) | |
| BBR | Glomerular mesangial cells, high glucose; podocytes | 50 and 100 µM, 24 h | Podocytes injury caused by exosomes derived from high-glucose-induced glomerular mesangial cells↓ | Inhibiting transfer of TGFβ1 from the glomerular mesangial cells to the podocytes through TGFβ1-PI3K/AKT pathway | (Wang et al., 2018c) | |
| BBR | SD rat, STZ + HFD | 100 and 200 mg/kg/day, 8 weeks | Histopathological changes↓; markers of kidney dysfunction↓ | ICAM-1 and VCAM-1 levels in the kidneys↓; β-arrestin 1 and β-arrestin 2↑ | (Tang et al., 2016) | |
| BBR | Wistar rats, STZ + HFD | 25 mg/kg/day, 20 weeks | Blood glucose↓; lipid deposition within the diabetic kidney↓; urinary excretion of albumin, thickening of GBM and renal fibrosis↓; | Pro-inflammatory cytokines (IL-1β, TNF-α) and chemokine (MCP-1) ↓; Smad3 signaling (FN, collagen I, collagen IV) and NF-κB signaling↓ | (Sun et al., 2015) | |
| BBR | Rat glomerular mesangial cells, high glucose | 30,90 µM, 24 h | Phospho-p38MAPK and phospho-CREB levels↓; FN and collagen synthesis↓ | (Liu et al., 2009) | ||
| BBR | Mesangial cells, high glucose | 10, 30, and 90 µM, 24 h | Mesangial cell area↓; high-glucose-induced cell cycle progression↓; proliferation and hypertrophy↓ | Cells in G1-phase↑ and in S-phase↓; p21(Waf1)/(Cip1) and p27(Kip1)↑; expressions of TGF-β1 and FN↓; transcription activity of NF-κB and AP-1↓ | (Lan et al., 2014) | |
| BBR | SD rat, STZ + HFD | 100 and 200 mg/kg/day, 6–8 weeks | Urine creatinine (UTP/C), BUN, and Cr levels↓; pathological changes, thickening of GBM, and mesangial matrix accumulation↓; inflammatory cell infiltration↓ | EP4, Gαs, and cAMP levels↑ | (Yang et al., 2014b) | |
| BBR | SD rat, STZ + HFD | 50, 100, and 200 mg/kg/day, 8 weeks | Restoring renal functional parameters; alterations in histological and ultrastructural changes↓ in the kidney tissues, glucose and lipid metabolism disorders↓ | Levels of IL-6 and PGE2↓; total protein expressions of EP1 and EP3 of renal cortex↓; expressions of EP4 and cAMP↑ | (Tang et al., 2014) | |
| BBR | Wistar rats, STZ | 100 and 200 mg/kg/day, 8 weeks | FBG↓; glomerular mesangial cells proliferation↓ | Gαs protein↑; Gαi protein↓; cAMP level↑; secretion of TGF-β, collagen IV ↓; FN and CTGF synthesis↓ | (Tang et al., 2013) | |
| BBR | SD rat, STZ + HFD | 100 and 200 mg/kg/day, 8 weeks | Restoring renal functional parameters, alterations in histological and ultrastructural changes↓ in the kidney tissues; glucose and lipid metabolism disorders↓ | cAMP level↑; protein expressions of GRK2 and GRK3↓; protein expressions of GRK6, GRK4↑; no significant change of GRK5 | (Wang et al., 2013a) | |
| BBR | Wistar rats, STZ | 200 mg/kg/day, 12 weeks | Glomerular area, glomerular volume, FBG, BUN, serum creatinine, and urine protein for 24h↓; MDA content↓; activity of SOD↑ | AR mRNA and protein in the kidney↓ | (Liu et al., 2008b) | |
| BBR | SD rat, STZ + HFD; podocytes, high glucose |
100 and 200 mg/kg/day, 8 weeks; 30 µM, 24 h |
Renal injury↓; ratio of kidney weight to body weight, 24 h urinary protein, serum creatinine, and BUN↓; systemic and renal cortex inflammatory response↓ | IL-1β, IL-6, and MCP-1 expression↓; protein level of TLR4 and phophorylation of IκBα and p65↓ | (Zhu et al., 2018) | |
| BBR | Wistar rats, STZ | 400 mg/kg/day, 12 weeks | Kidney injury↓; glomerular hypertrophy and mesangial matrix expansion↓ | mRNA and protein expressions of TGF-β, α-SMA, vimentin, NF-κB↓ | (Li and Zhang, 2017) | |
| BBR | KKAy mice; mouse renal tubular epithelial cells, high glucose | 150 mg/kg/day, 16 weeks; 30 µM, 48 h | Blood glucose and 24h urinary protein levels↓; degradation of renal function↓; normalization of an index of renal interstitial fibrosis and kidney weight/body weight; high-glucose-induced epithelial-to-mesenchymal transition events↓ | α-SMA↓; E-cadherin levels↑; protein and mRNA levels of jagged1, notch1, and hes1↓; snail protein and mRNA expressions↓ | (Yang et al., 2017a) | |
| BBR | SD rat, STZ + HFD | 150 mg/kg, 8 weeks | 24 h urinary microalbumin (mg) and urinary N-acetyl-glucosaminidase↓; renal tubulointerstitial injury↓ | Expressions of α-SMA, NF-κB, and MCP-1↓; E-cadherin levels↑ | (Ma et al., 2016c) | |
| BBR | C57BL/6J mice, STZ; NRK 52E cells, high glucose | 200 mg/kg/day, 12 weeks; 30 µM, 48 h |
Levels of FBG, Cr, BUN↓; renal fibrosis↓; epithelial-to-mesenchymal transition (EMT)↓ | Nrf2/HO-1/NQO1 pathway↑; phospho-Smad2/3 and collagen I↓; inhibiting TGF-β/Smad/EMT signaling activity in Nrf2-dependent manner | (Zhang et al., 2016) | |
| BBR | SD rats, STZ; mesangial cells, high glucose | 100 mg/kg/day, 8 weeks | Levels of UTP/C, BUN, and Cr↓; histopathological alterations↓; proliferation of mesangial cells↓ | Abnormal concentration of cytoplasmic Ca2+, level of PGE2, the high expressions of EP1 and Gαq↓ | (Ni et al., 2016) | |
| Diabetic encephalopathy | CR extract | SH-SY5Y human neuroblastoma cells, tert-butylhydroperoxide | 100 mg/ml, 2 and 24 h | Cell viability↑ | Mitochondrial membrane potential (MMP)↑; thioredoxin-interacting protein (TXNIP)↓ | (Friedemann et al., 2014) |
| Total alkaloids | SD rat, STZ + HFD | 80, 120, and 180 mg/kg/day, 24 weeks | Levels of FBG, glycosylated hemoglobin and glycosylated serum protein, FFA, TG, and TC↓; Aβ deposition↓; neuronal damage and loss↓; cognitive deficits↓ | The phosphorylation of IRS, PI3K, and Akt↑; overactivation of GSK3β↓; content of ApoA1↑ and ApoB↓ | (Li et al., 2018c) | |
| Pal | SD rat, STZ + HFD | 30 mg/kg/day (i.p.), 14 days | Hyperalgesia, allodynia, and depressive behaviors↓; activation of satellite glial cells after nervous injury stimulus↓ | Expressions of TNF-α and IL-1β in the hippocampus↓; colocalization of GFAP and P2X7 receptors ↓; phosphorylation of ERK1/2↓ | (Shen et al., 2018) | |
| BBR | Wistar rats, STZ + HFD | 100 mg/kg/day, 24 weeks | Body weight and blood levels of glucose↓; glycated hemoglobin, TG, TC↓; improved memory and affected evoked potential by decreasing latency | mRNA and protein expression of p38 and JNK↓; neuritin mRNA and protein levels↑; no effect on ERK1/2 protein | (Zhou et al., 2016) | |
| BBR | Wistar rat, STZ | 50 and 100 mg/kg/day, 8 weeks | Body weights↑; serum glucose↓; MDA and nitrite levels in hippocampal homogenates ↓; SOD levels↑; hyperglycemia↓; astrogliosis↓ | GFAP in the brain↓ | (Moghaddam et al., 2014) | |
| BBR | Wistar rat, STZ | 100 mg/kg/day, 12 weeks | Synaptic plasticity↑ | Hippocampal CA1 neuronal apoptosis↓; long-term potentiation (LTP) induction↑; paired pulse facilitation↓ | (Kalalian-Moghaddam et al., 2013; Moghaddam et al., 2013) | |
| BBR | SD rat, STZ + HFD; primary hippocampal neurons, high glucose | 100 and 200 mg/kg/day, 10 weeks; 0.05, 0.1 µM, 1 h | Hyperglycemia and insulin resistance↓; MDA levels↓; SOD levels↑; memory impairment↓ | Restoring PI3K/Akt/GSK3β signaling pathway; tau hyperphosphorylation↓ | (Wang et al., 2018b) | |
| BBR | Wistar rats, STZ + HFD | 187.5 mg/kg/day, 8 weeks | Inflammation mediator release and insulin resistance in medial prefrontal cortex↓; glucose uptake in the brain and metabolism of glucose in neuron↑; reinforcement of the information↑; cognitive impairment↓ | PI3K/Akt/mTOR↑; PKCη and PKCε and nuclear translocation of NF-κB in neuron↓; neuron-specific glucose transporter GLUT-3↑; amyloid precursor protein and BACE-1↓; production of oligomeric Aβ42↓ | (Chen et al., 2017b) | |
| BBR | SD rat, STZ; imprinting control region mice, STZ | 20 and 60 mg/kg/day, 2 weeks; 30 and 90 mg/kg/day, 2 weeks | Hyperglycemia-induced inflammatory reaction↓; heat hyperalgesia threshold↑ | Expressions of PKCε, TRPV1, TNF-α↓; inhibiting TRPV1 activation by blocking the PKC pathway | (Zan et al., 2017) | |
| BBR | db/db mice | 50 mg/kg/day, 10 weeks | Learning and memory ability↑; cognitive impairment↓; FBG, TG, TC, and LDL‐C↓; HDL‐C↑ | Synapse- and nerve-related protein expressions (PSD95, SYN, and NGF)↑; expressions of inflammatory factors (TNF-α and NF-κB) and ER stress-associated proteins (PERK, IRE-1α, eIF-2α, PDI, and CHOP) in the hippocampus↓; expression of SIRT1↑ | (Li et al., 2018b) | |
| BBR | SH-SY5Y cells, high glucose | 0.1–10 nM, 24 h | ROS production, nucleus condensation, and apoptosis↓; neurite outgrowth↑ | Bcl-2 expression↑; cytochrome c release↓; Nrf2 and HO-1↑; ROS production↓; Nrf2 siRNA abolished BBR-induced HO-1, NGF, neurite outgrowth and ROS decrease | (Hsu et al., 2013) | |
| BBR | Wistar rats, STZ | 25–100 mg/kg/day, 30 days | Cognitive performance↑; hyperglycemia and oxidative stress↓; MDA levels↓; GSH levels↑ | Choline esterase (ChE) activity in the cerebral cortex and hippocampus↓ | (Bhutada et al., 2011) | |
| BBR | SD rat, STZ + HFD; cerebral vascular smooth cells | 50, 100, and 200 mg/kg/day, 8 weeks | Glucose levels↓; Ca(2+)channel (CaL) current densities↓; resting intracellular Ca(2+) ([Ca(2+)]i) level↓ | α1C-subunit expressions of CaL↓; Ca(2+) releases from RyRs↓ | (Ma et al., 2016b) | |
| Diabetic osteopathy | BBR | SD rat, STZ+ HFD | 100 mg/kg/day, 12 weeks | Reabsorption and irregular histomorphometry↓; bone mineral density↑ | Serum osteocalcin and alkaline phosphatase (ALP) activity↑; TRAP↓; urinary 8-OHdG (DNA damage)↓; activities of SOD, catalase, glutathione peroxidase and GST↑ | (Xie et al., 2018) |
| BBR | Wistar albino rats, STZ+nicotinamide | 100 mg/kg/day, 12 weeks | Blood glucose↓; HbA1c levels↓; urinary calcium↓; bone histomorphometry↑ | Serum TRAP, mRNA expression of RANKL↓; PPAR-γ, Runx2, OPG, osteocalcin, and AMPK levels↑ | (Adil et al., 2017) | |
| Diabetic enteropathy | BBR | Wistar rats, STZ + HFD | 93.75, 187.5, and 375 mg/kg/day, 10 weeks | Fasting and postprandial blood glucose↓; insulin resistance index and TG↓; immune cells in mesenteric lymph nodes↑; intestinal barrier damage↓ | Intestinal TLR4, MyD88, and phosphorylation of IKKβ expressions↓; LBP and CD14 mRNA levels↓; IL-1β, MIF, and TNF-α mRNA ↓; IL-4 and IL-10 mRNA ↑ in intestinal tissue↑; secretion of GLP-1↑; production of GIP, amylin↑ and ghrelin↓ at high dose; OCLN, ZO-1 expressions↑; GFAP upregulation↓ | (Gong et al., 2017) |
| BBR | SD rat, STZ+ HFD | 100 mg/kg, 2 weeks | Restoration of intestinal villi/mucosa structure; infiltration of inflammatory cells↓; plasma LPS level↓ | Levels of ZO1 and GLP2↑ | (Shan et al., 2013) | |
| Diabetic retinopathy | BBR | Human retinal Müller cells+ native-LDL or HOG-LDL | 0–20 µM, 1 h | HOG-LDL-induced Müller cell injury↓; autophagy and apoptosis↓ | ATG-5 and beclin-1↓; ratio of LC3II/LC3I↓; cleaved PARR and cleaved caspase3↓; ROS production↓; expression of NOX4↓; expressions of Nrf2 and GPX-1↑; VEGF/PEDF ratio↓; protein levels of iNOS and ICAM-1↓; mRNA expressions of IL-6, IL-8, and TNF-α↓; AMPK expression↑ | (Fu et al., 2016) |
| BBR | Human retinal endothelial cells+ leukocytes freshly of non-diabetic or diabetic patients | 0–50 µM, 24 h | Leukocytes of diabetic patients mediated killing of retinal endothelial cells in vitro↓ | ICAM-1 (on endothelial cells) and CD18 (on leukocytes)↑; activation of NF-κB↓ and antioxidant enzymes (SOD, CAT, and GSH-Px)↑ in the retina | (Tian et al., 2013) | |
| Brb | Human retinal pigment epithelial cells, IL-1β or TNF-α | 1–25 µM, 30 min | IL-8 and MCP-1 expression↓; NF-κB translocation↓ | (Cui et al., 2006) |
↓ indicates inhibition/reduction while ↑ indicates increase/promotion; BBR, berberine; Cop, coptisine; Pal, palmatine; Jat, jatrorrhizine; Brb, berberrubine; Col, columbamine.