TABLE 1.
Recent animal studies on Chinese herbal medicines with anti-renal fibrosis function.
| Herbal/extract | Animal model | Outcome | Mechanism | Reference |
|---|---|---|---|---|
| Abelmoschus Manihot | 5/6 nephrectomy | ↓EMT | ↓PI3K-Akt-eNOS, ERK1/2 | Gu, et al. (2020); Peng, et al. (2016) |
| ADRN | ↓OX, inflammation | ↓ROS-ERK1/2-NLRP3 | Li, et al. (2019); Cai, et al. (2017) | |
| ↓NADPH oxidase/ROS/ERK | ||||
| UNE-ADR | ↓inflammation, glomerulosclerosis | ↓TNF-α,TGF-β1, p38MAPK | Tu, et al. (2013) | |
| STZ-DN mice | ↓OX | ↑AMPK-Sirt1-PGC-1 | Liao, et al. (2019) | |
| UNE-STZ-DN | ↓podocyte apoptosis | ↑PPAR-α/γ | Ge, et al. (2016); Liu, et al. (2017) | |
| ↓ iRhom2/TACE,ERS | ||||
| UNE-STZ-HFD-DN | ↓podocyte loss, FN | Regulating autophagy, mitochondrial dynamics | Kim, et al. (2018) | |
| UPPR rat | ↑intestinal microbiota | autophagy-mediated macrophage polarization | Tu, et al. (2020) | |
| ↓micro-inflammation | ||||
| Salvianolic Acid A, Tanshinone IIA | 5/6 nephrectomy | ↓OX, inflammation | ↑Akt/GSK-3β/Nrf2, BMP-7, Smad6 | Zhang, et al. (2019b); Zhang, et al. (2019a); Zhang, et al. (2018); Wang, et al. (2015b) |
| ↓NF-kB, p38 MAPK, TGF-β/Smads | ||||
| Salvianolic acid A | ADR-MCD rats | ↓proteinuria, podocyte injury | ↑PPAR-γ/Angptl4, Nrf2/HO-1 | Wang, et al. (2019b) |
| Tanshinone IIA | STZ-DN | ↓ERS, albuminuria | ↓PERK | (Xu, et al., 2020a) |
| ↓pathological damage | ↓OX, inflammation | Chen, et al. (2017) | ||
| Salvianolic Acid A | STZ-HFD-DN | ↓OX, inflammation, endothelial permeability; ↑autophagy | ↓AGE-RAGE-RhoA/ROCK, AGE-RAGE-Nox4 axis | Hou, et al. (2017) |
| Salvianolic Acid B | UUO rat | ↓pathological damage | ↓heparanase/syndecan 1 | Hu, et al. (2020) |
| Salvianolic Acid A, C | UUO rat | ↑renal function, tubular function | ↓CCL5 and CXCL10 | Li, et al. (2015) |
| ↓pathological damage | ||||
| Tanshinone IIA | AD-PO-UAN | ↓OX | ↓ NOX4, MAPK | Zhang et al. (2020c) |
| Salvianolic Acid B | RIRI rats | ↓OX, inflammation; caspase-1-mediated pyroptosis | ↑ PI3K/Akt; ↓ Nrf2 pathway | Ma et al., (2017b) |
| Pang, et al. (2020) | ||||
| Tanshinone IIA | ioversol-CIN | ↓tubular necrosis, apoptosis, OX | ↑ Nrf2/ARE activation | Liang, et al. (2018) |
| Tanshinone I | AAI-KI | ↓kidney injury | ↑cytochrome P450 1A | Feng, et al. (2013) |
| Salvianolic Acid B | FA-RTI mice | ↓tubular injury | ↓ ERS | Mai, et al. (2020) |
| Berberine | UUO rats | ↓ECM, inflammation, OX | ↓TGF-b1/Smad3 | Wang, et al. (2014) |
| DKD Murine | improve metabolism; ↓podocyte damage, glomerulosclerosis, mitochondrial dysfunction | ↓mitochondrial ROS | Qin, et al. (2020) | |
| ↑PGC-1α | ||||
| STZ-DN | ↓proteinuria, TIF, podocytes injury | ↑AMPK phosphorylation | Sun et al. (2015); Zhang et al. (2020b) | |
| ↓NF-k-light-chain-enhancer, TGFb1/Smad3 | Li and Zhang, (2017) | |||
| ↑Drp1 | Qin, et al. (2019) | |||
| STZ-DN | ↓inflammation | ↓TLR4/NF-kB | Sun et al. (2015) | |
| Zhu et al. (2018) | ||||
| STZ-DN | ↓ECM | ↓Nrf2; regulating MMPs/TIMPs | Ni, et al. (2015) | |
| STZ-DN | ↑renal pathology | ↑GRKs | Wang, et al. (2013) | |
| SHR | ↓hypertension, renal damage | ↓RAS, IL-6, IL-17, IL-23 | Guo, et al. (2015b) | |
| 2K1C-RV-HTN rats | ↓hypertension, sympathoexcitation | ROS/Erk1/2/iNOS | Tian, et al. (2019) | |
| tripterygium glycosides | NUE-STZ-DN | ↓glomerulosclerosis, TIF, microinflammation | ↓macrophage infiltration, TNF-a, IL-1b, TGF-b1, p38 MAPK, NF-kB | Wu, et al. (2017) |
| Triptolide | STZ-HFD-DN | ↓MA, inflammation, pathological damage | regulating Th cell balance | Guo et al. (2016) |
| ↓macrophage infiltration | ||||
| STZ-HFD-DN | ↓renal EMT | MiR-188-5p-PI3K/AKT | Xue et al. (2018) | |
| STZ-DN | ↓renal ECM | ↓microRNA-137/Notch1 | Han, et al. (2018) | |
| STZ-DN | restoring autophagy | ↓miR-141-3p/PTEN/Akt/mTOR | Li, et al. (2017b) | |
| UUO rats | ↓inflammatory, ECM; immune activity | ↓TGF-β1, CTGF, MCP1, osteopontin | Yuan, et al. (2011) | |
| PKD adult rats | ↓disease progression; ↑renal function | ↓JAK2-STAT3 | Jing, et al. (2018) | |
| DOCA-salt hypertension | ↓pathological damage | ↓inflammatory | Zhang, et al. (2020a) | |
| FSGS rats | ↓kidney injury, podocyte apoptosis | ↓ IL4 | Li, et al. (2020c) | |
| Puerarin | UUO murine | ↓ECM, TIF, epithelial cell apoptosis | ↓NOX4; ↓phosphorylation of p38, ERK, JNK, MAPK | Zhou, et al. (2017) |
| STZ-DM eNOS(−/−) mice | ↓OX, albuminuria, kidney injury | ↓NOX4↑; deacetylation of SIRT1-NF-κB | Li et al. (2017a); Xu, et al. (2020c) | |
| STZ-DN | ↓pathological damage, apoptosis | ↑miRNA-145-5p | Li et al. (2017a); Xu, et al. (2020c) | |
| ↓TLR4/MyD88/NF-κB (p65) | ||||
| STZ- DN mice | ↓UACR, kidney injury | ↑HMOX1, Sirt1-mediated podocyte autophagy | Li, et al. (2020b) | |
| STZ- DN rats | ↓kidney hypertrophy, OX, podocyte injury | ↑nephrin, podocin | Zhong, et al. (2014) | |
| ↓MMP9 | ||||
| STZ-DN mice | ↑autophagy, nephrin, podocin, podocalyxin | ↑ PERK/eIF2α/ATF4 | Xu et al. (2020b) | |
| ↓HIF-1alpha, VEGF | Shukla, et al. (2017) | |||
| STZ-DN rats | ↓renal AGEs contents | ↓AGEs, RAGE | Shen, et al. (2009) |
↑: increase or activation or improve; ↓: decrease or inhibition; AAI: aristolochic acid I; ADR: Adriamycin; ADRN: adriamycin nephropathy; AD-PO-UAN: adenine and potassium oxonate-induced uric acid nephropathy mice; AMPK: AMP-activated protein kinase; BMP-7: bone morphogenetic protein 7; CTGF: connective tissue growth factor; CIN: Contrast-Induced Nephropathy; DN: diabetic nephropathy; DM: diabetes mellitus; DKD: diabetic kidney disease; Drp1: dynamin-related protein 1; ECM: extracellular matrix; EMT: epithelial-mesenchymal transition; EMTD: epithelial-myofibroblast trans-differentiation; ERS: endoplasmic reticulum stress; eNOS(−/−): endothelial nitric oxide synthase-null mice; FA-RTI: fatty acids-induced renal tubular injury; FSGS: focal segmental glomerular sclerosis; GRKs: G protein-coupled receptor kinases; HFD: high-fat diet; KI: kidney injury; MMPs: matrix metalloproteinases; MCD: minimal change disease; NF: nuclear factor; NLRP3: NLR Family Pyrin Domain Containing 3; OX: oxidative stress; PGC-1: peroxisome proliferator-activated receptor-gamma coactivator-1; PKD: polycystic kidney disease; PO: potassium oxonate; PPAR: peroxisome proliferator-activated receptor; RIRI: renal ischemia-reperfusion injury; SHR: spontaneously hypertensive rats; STZ: Streptozotocin; STZ-DN: streptozotocin induced diabetic nephropathy; STZ-HFD-DN: streptozotocin induced and high-fat diet diabetic nephropathy; UACR: urinary albumin creatinine ratio; MA: urine micro-albumin; UNE: unilateral nephrectomy; UPPR: rat models were induced by uninephrectomy, potassium oxonate, and proinflammatory diet; UUO: unilateral ureteral obstruction; TIF: tubulointerstitial fibrosis; TIMPs: tissue inhibitor of metalloproteinases; TNF-a: tumor necrosis factor-a; TGF-b1: transforming growth factor-b1; 2K1C-RV-HTN:Two-kidney, one-clip renovascular hypertensive rats.