Table 2.

Applications of single herbal TCM and/or monomers in DN.

Name	Origins	Methods	Results	Pathways
Astragalus	Radix astragali	Human study (DN patients)	Decreasing BUN, Scr, and proteinuria and improving CCr and serum albumin level	[63]
		Type 2 diabetic animal study (KK-Ay mice)	Increasing Smad7 expression, inhibiting TGFβR-1, Smad3, and its phosphorylation expression, and decreasing TGF-β1 mRNA level	Rebalancing TGFβ/Smads signaling [64]
		Cellular study (kidney fibroblast)	Upregulating c-met expression	c-met pathway [65]
BBR	Coptis chinensis, Hydrastis Canadensis, Berberis aristata, Berberis aquifolium, and  Arcangelisia flava	Type 2 diabetic animal study (HFD + STZ induced rats)	Suppressing histological and ultrastructural changes in kidney, improving glucose and lipid metabolism disorder, increasing cAMP, downregulating GRK2 and GRK3, and upregulating GRK6	Modulating the expression of GRKs in G protein-AC-cAMP signaling pathway [66]
Curcumin	Curcuma longa L.(CLL)	Type 2 diabetic animal study (db/db mice)	Decreasing albuminuria and attenuating glomerular sclerosis	Inhibiting phosphorylation of STAT3 and degradation of IκB [67]
		Cellular study (mesangial cells)	Reducing AGE-induced oxidative stress and restoring AGE-induced mesangial cell apoptosis; Loganin inhibits FN and IL-6 expression	Reducing AGEs-induced ROS [68]
DMDD	Tuberous roots of A. carambola L.	Type 2 diabetic animal study (KK-Ay mice)	Decreasing hyperglycemia, renal AGE formation, RAGE, Scr, Ccr, and NF-κB, TGF-β1 and enhancing reduced SOD activities	Decreasing AGEs and TGF-β1 levels [69]
DP	Dragon's blood	Cellular study (human mesangial cells)	Preventing renal fibrosis	Inhibiting SGK1 and FN expression [70]
EGB	Ginkgo biloba leaves	Human study (DN patients)	Decreasing urinary mALB, α1-MG, IgG, TF, RBP, and NAG	Through decreasing sICAM-1 and sVCAM-1 [71, 72]
		Cellular study (mesangial cells)	Suppressing MC hypertrophy and ECM accumulation	Through TGF-β1 and Smads pathway [73]
FA	Seeds and leaves of plants	Type 1 diabetic animal study (OLETF rats)	Decreasing blood glucose and urinary ACR, mesangial matrix expansion, and glomerular basement thickness	Through reducing oxidative stress and inflammation [74, 75]
Flos A. manihot		Type 1 diabetic animal study (STZ induced rats)	Preventing renal damage and podocyte apoptosis	[76]
Genipin	Gardenia jasminoides	Type 1 diabetic animal study (STZ induced mice) Cellular study (mouse podocyte)	Ameliorating body weight loss and urine albumin leakage, attenuating GBM thickness, suppressing upregulation of UCP2, and restoring podocin and WT1 expression	Through suppressing upregulation of mitochondrial UCP2 [77]
HCT	Houttuynia Cordata Thunb.	Type 1 diabetic animal study (STZ induced rats)	Reducing UAER, Ccr, TGF-β1, and collagen I and increasing BMP-7	Decreasing TGF-β1 and increasing BMP-7 [78]
Icariin	Herba epimedii	Type 1 diabetic animal study (STZ induced rats)	Relieving renal damage	Inhibiting TGF-β1 and Col IV expression [79]
LAB	Salvia miltiorrhiza	Type 1 diabetic animal study (STZ induced rats)	Renal MDA↓, microalbuminuria↓, mesangial expansion↓, and glomerular hypertrophy↓	TGF-β1 pathway [80]
		Cellular study (mesangial cells)	TGF-β1 and fibronectin secretion↓ and PKC and ROS↓	PKC and ROS pathway [80]
		Cellular study (VSMCs)	Inhibiting VSMCs proliferation and migration	Nrf2-ARE-NQO1 [81]
LBP	Fruit of goji berry	Type 1 diabetic animal study (STZ induced rats)	Increasing antioxidant enzymes and increasing scavenging oxygen radicals	Via decreased ERK 1/2 activation through PKC [82]
LGP	Averrhoa carambola L. (Oxalidaceae) root	Type 1 diabetic animal study (STZ induced mice)	Decreasing hyperglycemia, NF-κB, caspase-3, caspase-8, caspase-9, and Bax expression; alleviating glomerular hypertrophy and ECM accumulation	[83]
Ligustrazine	Chuangxiong	Human study (DN patients)	Reducing BUN, Scr, 24 h urine protein, urine mAlb, and UAER	[84]
MC	Moutan cortex	Type 2 diabetic animal study (HFD + STZ induced rats)	Increasing SOD, GSH-PX, and CAT, reducing MDA; decreasing blood glucose, Scr, and urine protein and downregulating TGF-β2; decreasing IL-6 and MCP-1, TGF-β1, ICAM-1, and RAGE	Through attenuating oxidative stress and ameliorating inflammation [85–87]
		Cellular studies (HBZY-1 mesangial cell, rat mesangial cells)	Downregulating FN and collagen IV expression
Morroniside	Corni fructus	Type 1 diabetic animal study (STZ induced rats)	Increasing decreased serum ALB, reducing elevated BUN, and slowing down Ccr decrease	Through inhibiting hyperglycemia and oxidative stress [88]
PNS	Radixnotoginseng	Type 1 diabetic animal study (STZ induced rats)	Decreasing FBG, Ccr, UAlb, and renal index	Through inhibiting VEGF and TGF-β1 and enhancing BMP-7 and Smad7 [89, 90]
Puerarin	Pueraria candollei	Type 1 diabetic animal study (STZ induced rats)	Decreasing collagen IV; attenuating kidney hypertrophy, mesangial expansion, and proteinuria	Downregulating MMP-9 and eNOS expression [91–93]
Rhein	Rhubarb	Type 2 diabetic animal study (db/db mice)	Decreasing UAE and ECM levels, decreasing TGF-β1 and fibronectin deposition, and decreasing hyperlipidemia	Through decreasing lipid levels [94]
		Cellular study (rat renal PETCs)	Inhibiting cell hypertrophy	[95]
R. rosea	Rhodiola rosea	Type 2 diabetic animal study (HFD + STZ induced rats)	Reducing FBG, TC, TG, Ccr, and 24 h urinary albumin	Through decreasing TGF-β1 expression [96]
RLM	Rosa laevigata Michx.	Type 1 diabetic animal study (STZ induced rats)	Increasing SOD activity and total antioxidant capacity, decreasing MDA and ROS levels, and inhibiting NF-κB p65 and MCP-1 expression	Through regulating oxidative stress and inflammation [97]
Sequoyitol	Aristolochia arcuata, Amentotaxus yunnanensis, and Crossostephium chinense	Type 2 diabetic animal study (HFD + STZ induced rats)	Decreasing FBG, BUN, and Scr levels, increasing insulin and T-AOC levels in rats, and decreasing P22phox, P47phox, NF-κB, and TGF-β1 expression in vivo and in vitro	Through glucose-lowering effects, antioxidant activity, and regulation of TGF-β1 expression [98]
SF	Angelica sinensis, Lignsticum chuangxiong, Cimicifuga heracleifolia, and other plants	Human study (DN patients)	Lowering UAER level and improving renal function	Through decreasing (ET) and inhibiting the combination of ET with its receptor [99]
Skimmin	Hydrangea paniculata	Type 1 diabetic animal study (STZ induced rats)	Decreasing Scr and blood glucose level, alleviating glomerular segmental sclerosis and tubular vacuolar degeneration, and downregulating TGF-β1 and TGF-β1 receptor I expression	Through inhibiting TGF-β1 pathway [100]
SM	Salvia miltiorrhiza	Type 1 diabetic animal study (STZ induced rats)	Decreasing TGF-β1, CTGF, PAI-1, FN ED-1, collagen IV, and RAGE overexpression and protecting tubular function and structure	Through inhibiting TGF-β1 pathway, oxidative stress, and inflammation [101–103]
TGP	Paeonia lactiflora Pall.	Type 1 diabetic animal study (STZ induced rats)	Elevating antioxidant enzyme and decreasing p-p38 MAPK and NF-κB Decreasing Scr, BUN, and 24 h UP and improving renal histopathology	Through inhibiting oxidative stress [104]
		Type 2 diabetic animal study (HFD + STZ induced rats)		Through inhibiting Wnt/beta-catenin signaling pathway [105]
TMP	Ligusticum chuanxiong	Type 1 diabetic animal study (STZ induced rats)	Improving renal function	Through downregulating VEGF expression [106]
Triptolide	Diterpene purified from TwHF	Type 2 diabetic animal study (db/db mice)	Decreasing albuminuria, alleviating glomerular hypertrophy and podocyte injury, and attenuating inflammation and oxidative stress in kidney	Through inhibiting inflammation and dyslipidemia [107]
TwHF		Human study (DN patients)	Preventing podocyte injury	Downregulating TGF-β1, OPN, and CTGF [108]
VOMBP	Magnolia biondii Pamp.	Type 1 diabetic animal study (STZ induced rats)	Decreasing 24 UmAlb, sP-selectin in serum, and P-selectin in renal tissue	Inhibiting P-selectin [109]