Advances of traditional Chinese medicine preclinical mechanisms and clinical studies on diabetic peripheral neuropathy

Figures & data

Table 1. Single herbal extracts for the treatment of DPN.

Name	Extract source and Producer	Dose Range and Duration	Model	Control	Reference
Notoginsenoside R1	Panax notoginseng, brought from Sigma-Aldrich (St. Louis, MO)	10–100 μM for 48h, 50 μM was applied as optimum dosage	RSC96 cells	Vehicle	(Wang W et al. 2019)
Diosgenin	Dioscorea nipponica Makino, Solarbio Science & Technology Co., Ltd.,	50 and 100 mg/kg/day, i.g. for 8 weeks	Male C57 mice	Vehicle	(Leng et al. 2020)
Astragaloside IV	Astragali radix, Sigma-Aldrich, USA	Rats:20, 40 and 80 mg/kg/day, i.g. for 6 weeks Cells: 0,5,10,15 and 20μg/ ml for 48h	GK rats and RSC96 cells	Mecobalamin	(Yin et al. 2021)
Saikosaponin d	Radix Bupleuri, Chengdu Herbpurify Co., Ltd, Chengdu, China	1.0, 1.5 and 2.0 mg/kg/day, i.p. for 8 weeks	Male SD rats	Vehicle	(Xiang et al. 2023)
Salidroside	Rhodiola rosea, Tauto Biotech, Shanghai, China	50 and 100 mg/kg/day, i.g. for 6 weeks	Male SD rats	Vehicle	(Zheng et al. 2021)
Paeoniflorin	Paeonia lactiflora Pall. (Ranunculaceae), Liwah Pharmaceutical	Rats: 5.6 mg/kg/day for 12 weeks Cells: 10 μM for 24h	Male SD rats and RSC96 cells	Vehicle	(Yang X et al. 2022)
Gentiopicroside	Gentiana lutea, Nanjing Jingzhu Biological Science and Technology Co., Ltd., Nanjing, Jiangsu, China	50 and 100 mg/kg/day, i.g. for 2 weeks	Female SD rats	Oxcarbazepine	(Lu et al. 2018)
Curcumin	Curcuma longa L., Dalian Meilun Biotech Co., Ltd., Dalian, China	50, 100 and 150 mg/kg/day, i.g. for 4 weeks	Male SD rats	Vehicle	(Zhang WX et al. 2022)
Magnolol	Magnolia Officinalis J&K Scientific Ltd., Shanghai, China	15 and 30 mg/kg/day, i.g. for 4 weeks	Male C57BL/6 mice and db/db mice	Vehicle	(Yang J et al. 2022)
Honokiol	Magnolia Officinalis Aladdin, Shanghai, China	Rats: 25, 50 and 100 mg/kg/day, i.g. for 4 weeks Cells: 2.5, 5 and 10 μM for 48h	Male SD rats and RSC96 cells	α-lipoic acid	(Hu M et al. 2023)
Salvianolic acid A	Salvia miltiorrhiza Bunge (Lamiaceae) China Academy of Medical Sciences Institute of Medicine	0.3 and 1 mg/kg/day, i.g. for 8 weeks	KK-4Y mice	Valsartan	(Xu 2020)
Salvianolic acid B	Salvia miltiorrhiza Bunge (Lamiaceae) Sigma-Aldrich, St. Louis, MO, USA	0.1, 1 and 10 μM for 72h	RSC96 cells	Vehicle	(Wang J et al. 2019)
Resveratrol	Natural plants and fruits	10 ml/kg 10% resveratrol, i.g. for 12 weeks	CD1/ICR mice	Vehicle	(Zhang et al. 2021)
Vincamine	Madagascar periwinkle Absin, Shanghai, China	30 mg/kg/day, i.g. for 4 weeks	Male C57BL/6J mice and db/db mice	Vehicle	(Xu JW et al. 2023)
Lycorine	Lycoris radiate MCE Co., Monmouth Junction, NJ, USA	Rats: 20 mg/kg/ two days, i.g. for 3 weeks Cells: 0.96, 1.44, 2.87 and 5.74 μg/ml for 48h, 2.87μg/ml was applied as optimum dosage	C57BL/6 male mice and RSC96 cells	Vehicle	(Yuan et al. 2022)
Berberine	Rhizoma coptidis Sigma Aldrich (St.Louis, MO, USA)	Rats: 50 and 100 mg/kg/day, i.g. for 2 weeks Cells: 5 and 10 μM for 24h	Male SD rats and N2A neuroblastoma cells	Vehicle	(Yerra et al. 2018)
Jatrorrhizine	Rhizoma coptidis from Good Agricultural Practices Demonstration Base in Shizhu City (Chongqing, China), extracted by ethanol for 24h 3 times and then collected and evaporated to dryness under rotary evaporators to obtain the ethanol extract	Rats: 50,100 and 200 mg/kg/day, i.g. for 8 weeks Cels:10, 20 and 40 mM for 24h	db/db mice and RSC96 cells	Vehicle	(Gong et al. 2023)
Puerarin	Radix puerariae Phytomarker Ltd (Tianjin, China)	1, 10 and 100 μM for 48h	Schwann cells from the sciatic nerves of SD rats	Vehicle	(Wu et al. 2012)
Quercetin	Fruits and vegetables	50 mg/kg/day, i.g. for 12 weeks	Male SD rats	Vehicle	(Xie et al. 2020b)
Hedysarum polysaccharide	Hedysarum Weikeqi Biological Technology Company (Chengdu, China)	Rats: 50, 100 and 200 mg/kg/day, i.g. for 8 weeks Cells: 30, 60, 120 and 240 mg/L for 48h	Male ob/ob mice and Schwann cells from the sciatic nerves of SD rats	α-lipoic acid	(He et al. 2022)
Lycium barbarum polysaccharide	Lycium barbarum Ningxia Agricultural and Forestry College	100 and 500 mg/kg/day, i.g. for 12 weeks	Male SD rats	α-lipoic acid	(Liu et al. 2018)
Muscone	Musk Selleck Chemicals (Houston, TX, USA)	0.1, 1, 10 and 50 μM for 24, 48 and 72h	RSC96 cells	Vehicle	(Dong et al. 2019)

Table 2. TCM compound formula for the treatment of DPN(Preclinical).

Name	Recipe Composition	Extraction method	Dosage/Daily	Model	Effects	Reference
Tang-luo-ning	Astragali radix, Rehmannia glutinosa Libosch., Angelica sinensis(Oliv.)Diels, Lycium barbarum L., Achyranthes bidentata Bl., Chaenomeles speciosa(Sweet)Nakai, Dipsacus asper Wall. ex Henry, Codonopsis pilosula(Franch.)Nannf.	Prepare powder and dissolve the powder in distilled water	10.9 crude drug/kg/day and 21.8 crude drug/kg/day for 12 weeks	Male Sprague-Dawley (SD) rats	Oxidative and ER stress↓ Caspase-3, Bax↓	(Yang et al. 2017)
Mongolian prescriptions BAIMAI-SAN	picroside II, verbascose, taurine, ellagic acid, Borneolum syntheticum	/	0.1,0.3,0.9 mg/kg/day, i.g. for 75 days	Wistar rats	MNCV, SNCV↑	(Liu et al. 2011)
Jinmaitong	Cuscuta chinensis Lam., Ligustrum lucidum Ait., Herba Ecliptae, Prunella vulgaris L., Litchi chinensis Sonn., Cinnamomum cassia Presl, Corydalis yanhusuo W.T.Wang, Persicae semen, Cassiae semen, Asari radix et rhizome, Buthus martensii Karsch, Hirudo nipponica Whitman	After grounding into powder and mixing, per 100 mg powder is extracted in 1 mL of water and 1 mL of methanol.	0.4375 g/kg/day, 0.875 g/kg/day, and 1.75 g/kg/day for 8 weeks, 12 weeks or 16 weeks.	Male SD rats	①IGF-1, IGF-1R, gene P0 and PMP22↑ Active Wnt/β-catenin pathway	①(Song et al. 2019) ②(Song et al. 2021)
Jiaweibugan decoction	Lycium barbarum L., Chaenomeles speciosa (Sweet)Nakai, Angelica sinensis (Oliv.) Diels, Ligusticum chuanxiong Hort., Rehmanniae radix praeparata, Paeonia lactiflora Pall., Taxillus chinensis (DC.) Danser, Ophiopogon japonicus(L.f)Ker-Gawl., Trichosanthis radix	Decoct with 1 200 mL water 30 min, warm on low heat twice 30 min.	28.6 g/kg per day for 8 weeks.	Male Wistar rats	MDA, NF-kB p65 mRNA and p38 mitogen-activated protein kinase ↓; GSH↑	(Wang et al. 2013)
Huangqi Guizhi Wuwu decoction	Astragali radix, Cinnamomum cassia Presl, Paeonia lactiflora Pall., Zingiber officinale Rosc., Ziziphus jujuba Mill.	/	①10% Medicated serum ②3.5 g/kg, 7 g/kg and 14 g/kg for 8 weeks	①RSC96 cells ②db/db mice	①ROS↓;T-SOD↑ ②TNF-α, IL-1β and IL-6, MDA↓ IL-10, GSH, T-SOD and NGF↑	①(Gao 2022) ②(Zhang et al. 2024)
Modified Huangqi Guizhi Wuwu Decoction	Astragali radix, Cinnamomum cassia Presl, Paeonia lactiflora Pall., Ligustrum lucidum Ait., Corydalis yanhusuo W.T.Wang, Coptis chinensis Franch., Spatholobus suberectus Dunn, Hirudo nipponica Whitman	Chinese medicinal granules are prepared with distilled water.	1.25g/kg/d and 2.5g/kg/d	Male SD rats	①Bax, Caspase-12↓ ②ROS, p-IRE1α and CHOP↓	①(Zhang et al. 2023a) ②(Zhang et al. 2023b)
Danggui Sini Decoction	Angelica sinensis (Oliv.) Diels, Cinnamomum cassia Presl, Asari radix et rhizome, Paeonia lactiflora Pall., Tetrapanax papyrifer(Hook.)K.Koch, Ziziphus jujuba Mill., Glycyrrhizae radix et rhizoma	Decocting	1.84 g/kg/d and 7.36 g/kg/d for 8 weeks	Wistar rats	MNCV↑; NF-κB↓	(Cheng et al. 2019)
Long-Qi Decoction	Cinnamomum cassia Presl, Morus alba L., Angelica sinensis(Oliv.)Diels, Astragali radix, Paeoniae radix rubra, Pheretima, Spatholobus suberectus Dunn	Heat and reflux for 2h, add ethanol, take the supernatant and concentrate it, then grind it into power.	1.58g/kg,3.17g/kg and 6.33g/kg,	Male Wistar rats	NCV↑; Sorbitol and aldose reductase↓	(He et al. 2019)
Tangtong Formula	Astragali radix, Cinnamomum cassia Presl, Paeonia lactiflora Pall., Asari radix et rhizome, Eupolyphaga steleophaga, Curcuma longa L., Ligusticum chuanxiong Hort.	Decocting	9.17g/kg/d, 18.33g/kg/d and 36.67 g/kg/d	SD rats	MNCV, SNCV↑	①(Wei et al. 2019) ②(He 2021)
Yiqi Huoxue Tongluo Formula	Astragali radix, Angelica sinensis(Oliv.)Diels, Rehmannia glutinosa Libosch., Paeonia lactiflora Pall., Persicae semen, Carthamus tinctorius L., Achyranthes bidentata Bl., Paeoniae radix rubra, Spatholobus suberectus Dunn, Chaenomeles speciosa(Sweet)Nakai, Caesalpinia sappan L., Corydalis yanhusuo W.T.Wang, Glycyrrhizae radix et rhizoma praeparata cum melle	Soaking, decocting, filtering, and concentrating	1.84 g/kg/d and 7.36 g/kg/d for 8 weeks	Wistar rats	MNCV↑; NF-κB↓	(Zhang L et al. 2022)
Tang Bi Kang (TBK) granule	Astragali radix, Ligustrum lucidum Ait., Cinnamomum cassia Presl, Paeonia lactiflora Pall., Spatholobus suberectus Dunn, Scutellaria baicalensis Georgi, Coptis chinensis Franch., Hirudo nipponica Whitman, Corydalis yanhusuo W.T.Wang	Soak 1h, decoct thrice for 2h each, add alcohol to concentrate, reflux-extracted thrice for 1h each.	4.28g/kg, 8.56g/kg and 17.12g/kg for 4 weeks	Wistar rats	FBG, TNF-αand IL-6, MDA↓ MNCV, SNCV, SOD and GSH-pX↑	①(Yang, XW et al. 2015) ②(Liu G et al. 2023)
Compound XiongShao Capsule	Paeonia lactiflora Pall., Cyathula officinalis Kuan, Ligusticum chuanxiong Hort., litchi rind, Saposhnikovia divaricate (Turcz.)Schischk., Cinnamomum cassia Presl, Sargassum, Polygonatum sibiricum Red., Astragali radix, Morus alba L., Silybum marianum(L.)Gaertn., Orostachys fimbriata(Turcz.)Berg.	Decoct first for 2h with distilled water eight times and then for 1h with distilled water six times.	0.12 g/kg, 0.36 g/kg and 1.2 g/kg for 8 weeks	Male SD rats	NCV, SOD↑; Bax, caspase-3, AGEs and NOS↓	(Yu et al. 2021)
Compound Qiying Granule	Astragali radix, Polygonatum sibiricum Red., Salvia miltiorrhiza Bge., Cryptotympana pustulata Fabricius, chickpea	/	1.17 g/kg/d, 2.34 g/kg/d and 4.68 g/kg/d for 4 weeks	Male Wistar rats	IL-6, IL-1β, TNF-α and ROS↓	(Hu Y et al. 2023)
Liuweiluobi granule	Hippophae rhamnoides L., Carthamus tinctorius L., Lonicerae japonicae Flos, Scutellaria barbata D.Don, Achyranthes bidentata Bl., Ephedra sinica Stapf	/	4.4g/kg, 8.7g/kg and 17.4g/kg for 12 weeks	Male db/db mice	FGB↓ MNCV, SNCV↑	(Liu 2021)
Chaihu Shugan Power	Bupleurum chinense DC., Citrus reticulata Blanco, Paeonia lactiflora Pall., Citrus aurantium L., Ligusticum chuanxiong Hort., Cyperus rotundus L., Glycyrrhizae radix et rhizoma praeparata cum melle	Soak 2 h, decoct twice, mix and filter, and concentrate by water bath evaporation to obtain concentrated medicine.	3.15g/kg,6.30g/kg and 12.60 g/kg for 8 weeks	Male SD rats	MNCV, TRPV1, CGRP, TNF-α and IL-1β↑	(Wang Y et al. 2023)
QiGui TangTongNing Granule	Astragali radix, Angelica sinensis (Oliv.) Diels, Rehmannia glutinosa Libosch., Pueraria lobata(Willd.)Ohwi, Corydalis yanhusuo W.T.Wang, Spatholobus suberectus Dunn, Clematis chinensis Osbeck	/	1.575g/kg/d, 3.15 g/kg/d and 6.30 g/kg/d for 12 weeks	Male SD rats	NCV, PWMT↑ AGEs↓	(Liu 2020)

Table 3. TCM compound formula for the treatment of DPN(clinical).

Name	Recipe Composition	Extraction method	Manufacturer	Dosage	Duration	Reference
Danggui Sini Decoction	Angelica sinensis(Oliv.)Diels, Spatholobus suberectus Dunn, Pheretima, Glycyrrhizae radix et rhizoma praeparata cum melle, Asari radix et rhizoma, Paeonia lactiflora Pall., Astragali radix, Tetrapanax papyrifer(Hook.)K.Koch, Ziziphus jujuba Mill.	Soak 10 min, decoct with 400ml water 20 min to keep 200ml, add 300ml water to decoct again and keep 150 ml medicinal juice, mix the juice and decoct.	The Research Department	350ml/d	4 weeks	(Cao 2018)
Modified Danggui Sini Decoction	Astragali radix praeparata cum melle, Paeonia lactiflora Pall., Spatholobus suberectus Dunn, Angelica sinensis (Oliv.) Diels, Cinnamomum cassia Presl, Pheretima, Asari radix et rhizoma, Tetrapanax papyrifer(Hook.)K.Koch, Glycyrrhizae radix et rhizoma, Ziziphus jujuba Mill., Scolopendra subspinipes mutilans L.Koch	Decoct with 300ml water.	The Research Department	300ml/d	4 weeks	(Yang 2017a)
Modified Danggui Sini Decoction	Angelica sinensis (Oliv.) Diels, Paeonia lactiflora Pall., Asari radix et rhizoma, Cinnamomum cassia Presl, Tetrapanax papyrifer(Hook.)K.Koch, Ziziphus jujuba Mill., Glycyrrhizae radix et rhizoma praeparata cum melle	Decocting	The Research Department	1 dose/d	4 weeks	(Chen 2018)
Xiaoketongbi Formula	Persicae semen, Rheum officinale Baill., Astragali radix, Angelica sinensis (Oliv.) Diels, Salvia miltiorrhiza Bge.	Extracted with hot water, concentrated, spray‐dried, processed into granules	Huarun Sanjiu Pharmaceuticals Co Ltd.	15 g/d for 10 weeks	10 weeks	(Lu et al. 2022)
Fuyan Tongluo Decoction	Aconitum carmichaelii Debx., Lonicera japonica Thunb., Atractylodes macrocephala Koidz., Asari radix et rhizome, Angelica sinensis (Oliv.) Diels, Glycyrrhizae radix et rhizoma praeparata cum melle	Decocting	Shanxi Provincial Integrated TCM And WM Hospital	150ml/twice/d	8 weeks	(Zhang et al. 2019b)
Modified Huangqi Guizhi Wuwu Decoction	Astragali radix, Paeonia lactiflora Pall., Pueraria lobata (Willd.) Ohwi, Salvia miltiorrhiza Bge., Cinnamomum cassia Presl, Ligusticum chuanxiong Hort., Angelica sinensis(Oliv.)Diels	Soak 20-30 min, boil and then decoct with slow fire for 20-30 min to keep 200-300 ml juice.	The Research Department	200∼300 mL/d	/	(Cheng et al. 2020)
Tangmoning Decoction	Astragali radix, Rehmannia glutinosa Libosch., Angelica sinensis (Oliv.) Diels, Ligusticum chuanxiong Hort., Cinnamomum cassia Presl, Cornus officinalis Sieb.et Zucc., Persicae semen, Pheretima, Paeoniae radix rubra, Achyranthes bidentata Bl., Spatholobus suberectus Dunn, Salvia miltiorrhiza Bge., Glycyrrhizae radix et rhizoma, Lycium barbarum L., Panax ginseng C.A.Mey., Corydalis yanhusuo W.T.Wang, Clematis chinensis Osbeck	Decoct to keep 400ml juice.	The Research Department	400ml/d	A month	①(Chen and Zhang 2023) ②(Zhang 2020)
Huangqi Danshen Tongluo formula	Astragali radix, Salvia miltiorrhiza Bge., Cinnamomum cassia Presl, Angelica sinensis (Oliv.)Diels, Spatholobus suberectus Dunn, Pheretima	Decoct in water for 2 times/20 min and leave 500 ml juice.	The Research Department	500ml/d	4 weeks	(Shi 2019)
Buyang Huanwu Decoction	Astragali radix, Cinnamomum cassia Presl, Achyranthes bidentata Bl., Eupolyphaga steleophaga, Angelica sinensis(Oliv.)Diels, Ligusticum chuanxiong Hort., Salvia miltiorrhiza Bge., Paeonia lactiflora Pall., Persicae semen, Carthamus tinctorius L., Curcuma longa L., Glycyrrhizae radix et rhizome, Ziziphus jujuba Mill.	Decoct in water 2 times and mix the juice.	The Research Department	Twice/d	4 weeks	(Li 2021)
Yiqi Huoxue Tongluo formula	Astragali radix, Dendrobll caulis, Scrophularia ningpoensis Hemsl., Spatholobus suberectus Dunn, Cinnamomum cassia Presl, Angelica sinensis (Oliv.)Diels, Paeonia lactiflora Pall., Pheretima, Clematis chinensis Osbeck, Cyathula officinalis Kuan, Glycyrrhizae radix et rhizoma	Boil with strong fire, then decoct with slow fire.	The Research Department	1 dose/d	30 days	(Zhou 2019)
Qiteng Tongluo Yin	Astragali radix, Salvia miltiorrhiza Bge., Cinnamomum cassia Presl, Angelica sinensis (Oliv.) Diels, Spatholobus suberectus Dunn, Pheretima	Decoct to keep 300ml.	The Research Department	300 mL/d	12 weeks	(Yang et al. 2019)
Fuyuan Huoxue Decoction	Guaweigen, Rheum officinale Baill., Angelica sinensis (Oliv.) Diels, Glycyrrhizae radix et rhizome, Bupleurum chinense DC., Persicae semen, Carthamus tinctorius L., Pangolin Scales	Decoct to keep 300ml.	The Research Department	300ml/d for 2 or 4 weeks	2 or 4 weeks	①(Zhang and Zhang 2018) ②(Zhang 2018)
Wenyang Huoxue Tongluo recipe	Astragali radix, Spatholobus suberectus Dunn, Rehmanniae radix praeparata, Ligusticum chuanxiong Hort., Cyathula officinalis Kuan, Paeoniae radix rubra, Psoralea corylifolia L., Carthamus tinctorius L., Paeonia lactiflora Pall., Curcuma rhizome, Cinnamomum cassia Presl, Cinnamomum cassia Presl, Asari radix et rhizoma	Decocting	The Research Department	1 dose/d	/	(Zhou 2017)
Yiqi Huoxue Decoction	Astragali radix, Trichosanthis radix, Atractylodis rhizome, Salvia miltiorrhiza Bge., Angelica sinensis (Oliv.) Diels, Dioscorea opposita Thunb., Spatholobus suberectus Dunn, Bombyx batryticatus, Rehmanniae radix praeparata, Pheretima, Morus alba L.	Decocting	The Research Department	1 dose/d	2 month	(Yang 2017b)
Qidan Dihuang Decoction	Astragali radix, Salvia miltiorrhiza Bge., Rehmannia glutinosa Libosch., Fruit of Cornus officinalis Sieb.rt Zucc., Dioscorea opposita Thunb., Alisma plantago-aquatica Linn., Tree Peony Bark, Poria cocos (Schw.) Wolf, Spatholobus suberectus Dunn, Cinnamomum cassia Presl, Dendrobll caulis, Cyathula officinalis Kuan, Panax notoginseng(Burk.)F.H.Chen	Decocting	The Research Department	1 dose/d	2 month	(Wang and Lu 2017)
Modified Taohong Siwu Decoction	Persicae semen, Carthamus tinctorius L., Ligusticum chuanxiong Hort., Rehmanniae radix praeparata, Paeonia lactiflora Pall., Angelica sinensis (Oliv.) Diels, Codonopsis pilosula (Franch.)Nannf., Astragali radix	Decoct to keep 150ml juice.	The Research Department	300ml/d	2 month	(Peng et al. 2023)
Tangshen’an decoction	Astragali radix, Morus alba L., Pueraria lobata (Willd.) Ohwi, Salvia miltiorrhiza Bge., Achyranthes bidentata Bl., Dung of Trogopterus xanthipes Milne-Edwards, Olibanum, Cinnamomum cassia Presl, Commiphora myrrha Engl., Zaocys dhumnades(Cantor), huaPanax notoginseng(Burk.)F.H.Chen, Buthus martensii Karsch	Decoct with 450ml water.	The Research Department	450mL/d	1 month	(Wu 2021)
Jiangtang Tongmailing Capsule	Panax quinquefolium L., Astragali radix, Cornus officinalis Sieb.et Zucc., Lycium barbarum L., Ligusticum chuanxiong Hort., Angelica sinensis (Oliv.) Diels, Salvia miltiorrhiza Bge., Paeonia lactiflora Pall., Polygonatum sibiricum Red., Pangolin Scales, Achyranthes bidentata Bl., Morus alba L., Cinnamomum cassia Presl	/	The Research Department	15capsules/d	2 month	(Mu 2016)
Danshen and Gergen granule	Pueraria lobata (Willd.) Ohwi, Salvia miltiorrhiza Bge.	/	The Research Department	1 dose/d	2 month	(Wen 2017)
Compound Xiongshao Capsule	Paeonia lactiflora Pall., Cyathula officinalis Kuan, Ligusticum chuanxiong Hort., litchi rind, Saposhnikovia divaricate (Turcz.) Schischk., Cinnamomum cassia Presl, Sargassum, Polygonatum sibiricum Red., Astragali radix, Morus alba L., Silybum marianum(L.)Gaertn., Orostachys fimbriata(Turcz.)Berg.	/	Shanghai fangxin pharmacy technology co., ltd	0.9 g, tid	6 month	(Cui et al. 2018)
Jiangtang Huoluo pill	Panax ginseng C.A.Mey, Ophiopogon japonicus(L.f)Ker-Gawl., Schisandra chinensis(Turcz.)Baill, Trichosanthis radix, Dioscorea nipponica Makino., Angelica sinensis(Oliv.)Diels, Paeonia suffruticosa Andr., Scrophularia ningpoensis Hemsl., Salvia miltiorrhiza Bge., Morus alba L., Zaocys dhumnades(Cantor), Pheretima, Scolopendra subspinipes mutilans L.Koch, Gallus gallus domesticus Brisson	/	The Research Department	9g, tid	4 weeks	(Wu et al. 2019)

Figure 1. Mechanisms and representative drugs of TCM in treating DPN. Inflammation (blue): alleviated through AMPK, GPR40, TLR4 and PPARγ signal pathways. Oxidative stress and apoptosis (red): inhibit oxidative stress, and apoptosis through Keap1/Nrf2 and PI3K/AKT pathways. Mitochondrial dysfunction (purple): the regulation of mitochondria can be divided into mitochondrial biogenesis, dynamics, oxidative stress and autophagy. Endoplasmic reticulum stress (green): TCM inhibits endoplasmic reticulum stress through the IRE1α/XBP1/CHOP signaling pathway. AMPK: the adenosine 5′-monophosphate (AMP)-activated protein kinase; GPR40: G protein-coupled receptor 40; TLR4: Toll-like receptor 4; PPAR: the peroxisome proliferator-activated receptor; Nrf2: the nuclear factor erythroid 2-related factor 2; PI3K: Class I phosphoinositide 3-kinase; AKT: serine/threonine kinase; Keap1: Kelch-like ECH-associating protein 1; IRE1α: inositol requiring enzyme 1; XBP1: X-box binding protein1; CHOP: CCAAT/enhancer binding protein homologous protein.

Figure 2. Mechanisms of traditional chinese medicine in treating DPN by improving mitochondrial dysfunction, including mitochondrial biogenesis (①), mitochondrial dynamics (② and ③), mitochondrial oxidative stress (④) and mitochondrial autophagy (⑤) (by figdraw). PGC-1α: PPARγ coactivator-1α; AMPK: the adenosine 5′-monophosphate (AMP)-activated protein kinase; NRF1 and NRF2: nuclear respiratory factors 1 and 2; TFAM: the mitochondrial transcription factor A; SIRT1: Sirtuin 1; Drp1: dynamin-related protein 1; Mfn1/2: mitochondrial protein 1/2; Opa1: Optic atrophy 1; AGEs: advanced glycosylation end products; PINK1: PTEN-inducible kinase 1; parkin: Parkinson’s disease protein.

Wang W, Hao Y, Li F. 2019. Notoginsenoside R1 alleviates high glucose-evoked damage in RSC96 cells through down-regulation of miR-503. Artif Cells Nanomed Biotechnol. 47(1):3947–3954. doi:10.1080/21691401.2019.1671434.

 PubMed Web of Science ®Google Scholar

Leng J, Li X, Tian H, Liu C, Guo Y, Zhang S, Chu Y, Li J, Wang Y, Zhang L. 2020. Neuroprotective effect of diosgenin in a mouse model of diabetic peripheral neuropathy involves the Nrf2/HO-1 pathway. BMC Complement Med Ther. 20(1):126. doi:10.1186/s12906-020-02930-7.

 PubMedGoogle Scholar

Yin Y, Qu H, Yang Q, Fang Z, Gao R. 2021. Astragaloside IV alleviates Schwann cell injury in diabetic peripheral neuropathy by regulating microRNA-155-mediated autophagy. Phytomedicine. 92:153749. doi:10.1016/j.phymed.2021.153749.

 PubMed Web of Science ®Google Scholar

Xiang Q, Liu Y, Chen L. 2023. Saikosaponin D (SSD) alleviates diabetic peripheral neuropathy by regulating the AQP1/RHOA/ROCK signaling in streptozotocin-induced diabetic rats. Acta Diabetol. 60(6):805–815. doi:10.1007/s00592-023-02060-9.

 PubMed Web of Science ®Google Scholar

Zheng T, Wang Q, Bian F, Zhao Y, Ma W, Zhang Y, Lu W, Lei P, Zhang L, Hao X, et al. 2021. Salidroside alleviates diabetic neuropathic pain through regulation of the AMPK-NLRP3 inflammasome axis. Toxicol Appl Pharmacol. 416:115468. doi:10.1016/j.taap.2021.115468.

 PubMed Web of Science ®Google Scholar

Yang X, Li X, Zhu Y, Gao Y, Xu L. 2022. Paeoniflorin upregulates mitochondrial thioredoxin of Schwann cells to improve diabetic peripheral neuropathy indicated by 4D label-free quantitative proteomics. Oxid Med Cell Longev. 2022:4775645. doi:10.1155/2022/4775645.

 PubMed Web of Science ®Google Scholar

Lu Y, Yao J, Gong C, Wang B, Zhou P, Zhou S, Yao X. 2018. Gentiopicroside ameliorates diabetic peripheral neuropathy by modulating PPAR-γ/AMPK/ACC signaling pathway. Cell Physiol Biochem. 50(2):585–596. doi:10.1159/000494174.

 PubMedGoogle Scholar

Zhang WX, Lin ZQ, Sun AL, Shi YY, Hong QX, Zhao GF. 2022. Curcumin ameliorates the experimental diabetic peripheral neuropathy through promotion of NGF expression in rats. Chem Biodivers. 19:e202200029.

 PubMed Web of Science ®Google Scholar

Yang J, Wei Y, Zhao T, Li X, Zhao X, Ouyang X, Zhou L, Zhan X, Qian M, Wang J, et al. 2022. Magnolol effectively ameliorates diabetic peripheral neuropathy in mice. Phytomedicine. 107:154434. doi:10.1016/j.phymed.2022.154434.

 PubMed Web of Science ®Google Scholar

Hu M, Jiang W, Ye C, Hu T, Yu Q, Meng M, Sun L, Liang J, Chen Y. 2023. Honokiol attenuates high glucose-induced peripheral neuropathy via inhibiting ferroptosis and activating AMPK/SIRT1/PGC-1α pathway in Schwann cells. Phytother Res. 37(12):5787–5802. doi:10.1002/ptr.7984.

 PubMed Web of Science ®Google Scholar

Xu C. 2020. Protective effect and mechanism of salvianolic acid A on diabetic peripheral neuropathy [master’s thesis]. Harbin Univ Commerce.

 Google Scholar

Wang J, Wang L, Lou GH, Zeng HR, Hu J, Huang QW, Peng W, Yang XB. 2019. Coptidis rhizoma: a comprehensive review of its traditional uses, botany, phytochemistry, pharmacology and toxicology. Pharm Biol. 57(1):193–225. doi:10.1080/13880209.2019.1577466.

 PubMed Web of Science ®Google Scholar

Zhang W, Yu H, Lin Q, Liu X, Cheng Y, Deng B. 2021. Anti-inflammatory effect of resveratrol attenuates the severity of diabetic neuropathy by activating the Nrf2 pathway. Aging (Albany NY). 13(7):10659–10671. doi:10.18632/aging.202830.

 PubMedGoogle Scholar

Xu JW, Xu X, Ling Y, Wang YC, Huang YJ, Yang JZ, Wang JY, Shen X. 2023. Vincamine as an agonist of G-protein-coupled receptor 40 effectively ameliorates diabetic peripheral neuropathy in mice. Acta Pharmacol Sin. 44(12):2388–2403. doi:10.1038/s41401-023-01135-1.

 PubMed Web of Science ®Google Scholar

Yuan Q, Zhang X, Wei W, Zhao J, Wu Y, Zhao S, Zhu L, Wang P, Hao J. 2022. Lycorine improves peripheral nerve function by promoting Schwann cell autophagy via AMPK pathway activation and MMP9 downregulation in diabetic peripheral neuropathy. Pharmacol Res. 175:105985. doi:10.1016/j.phrs.2021.105985.

 PubMed Web of Science ®Google Scholar

Yerra VG, Kalvala AK, Sherkhane B, Areti A, Kumar A. 2018. Adenosine monophosphate-activated protein kinase modulation by berberine attenuates mitochondrial deficits and redox imbalance in experimental diabetic neuropathy. Neuropharmacology. 131:256–270. doi:10.1016/j.neuropharm.2017.12.029.

 PubMed Web of Science ®Google Scholar

Gong X, Gui Z, Ye X, Li X. 2023. Jatrorrhizine ameliorates Schwann cell myelination via inhibiting HDAC3 ability to recruit Atxn2l for regulating the NRG1-ErbB2-PI3K-AKT pathway in diabetic peripheral neuropathy mice. Phytother Res. 37(2):645–657. doi:10.1002/ptr.7641.

 PubMed Web of Science ®Google Scholar

Wu Y, Xue B, Li X, Liu H. 2012. Puerarin prevents high glucose-induced apoptosis of Schwann cells by inhibiting oxidative stress. Neural Regen Res. 7(33):2583–2591. doi:10.3969/j.issn.1673-5374.2012.33.003.

 PubMed Web of Science ®Google Scholar

Xie J, Song W, Liang X, Zhang Q, Shi Y, Liu W, Shi X. 2020b. Protective effect of quercetin on streptozotocin-induced diabetic peripheral neuropathy rats through modulating gut microbiota and reactive oxygen species level. Biomed Pharmacother. 127:110147. doi:10.1016/j.biopha.2020.110147.

 PubMed Web of Science ®Google Scholar

He L, Huan P, Xu J, Chen Y, Zhang L, Wang J, Wang L, Jin Z. 2022. Hedysarum polysaccharide alleviates oxidative stress to protect against diabetic peripheral neuropathy via modulation of the Keap1/Nrf2 signaling pathway. J Chem Neuroanat. 126:102182. doi:10.1016/j.jchemneu.2022.102182.

 PubMed Web of Science ®Google Scholar

Liu SY, Chen L, Li XC, Hu QK, He LJ. 2018. Lycium barbarum polysaccharide protects diabetic peripheral neuropathy by enhancing autophagy via mTOR/p70S6K inhibition in streptozotocin-induced diabetic rats. J Chem Neuroanat. 89:37–42. doi:10.1016/j.jchemneu.2017.12.011.

 PubMed Web of Science ®Google Scholar

Dong J, Li H, Bai Y, Wu C. 2019. Muscone ameliorates diabetic peripheral neuropathy by activating the Akt/mTOR signalling pathway. J Pharm Pharmacol. 71(11):1706–1713. doi:10.1111/jphp.13157.

 PubMed Web of Science ®Google Scholar

Yang X, Yao W, Liu H, Gao Y, Liu R, Xu L. 2017. Tangluoning, a traditional Chinese medicine, attenuates in vivo and in vitro diabetic peripheral neuropathy through modulation of PERK/Nrf2 pathway. Sci Rep. 7(1):1014. doi:10.1038/s41598-017-00936-9.

 PubMedGoogle Scholar

Liu QS, Pang ZR, Liu R, He GR, Cui J, Yin XY. 2011. Effective compounds group of Mongolian prescriptions BAIMAI-SAN protect against peripheral neuropathy in lower limbs of rats through neuro protective effect. J Ethnopharmacol. 135(3):786–791. doi:10.1016/j.jep.2011.04.026.

 PubMed Web of Science ®Google Scholar

Song W, Jiang W, Wang C, Xie J, Liang X, Sun Y, Gong L, Liu W, Qu L. 2019. Jinmaitong, a traditional Chinese compound prescription, ameliorates the streptozocin-induced diabetic peripheral neuropathy rats by increasing sciatic nerve IGF-1 and IGF-1R expression. Front Pharmacol. 10:255. doi:10.3389/fphar.2019.00255.

 PubMed Web of Science ®Google Scholar

Song W, Sun Y, Liang XC, Zhang Q, Xie J, Wang C, Liu W. 2021. Jinmaitong ameliorates diabetes-induced peripheral neuropathy in rats through Wnt/β-catenin signaling pathway. J Ethnopharmacol. 266:113461. doi:10.1016/j.jep.2020.113461.

 PubMed Web of Science ®Google Scholar

Wang Y, Chen Z, Ye R, He Y, Li Y, Qiu X. 2013. Protective effect of jiaweibugan decoction against diabetic peripheral neuropathy. Neural Regen Res. 8(12):1113–1121. doi:10.3969/j.issn.1673-5374.2013.12.006.

 PubMed Web of Science ®Google Scholar

Gao Y. 2022. Syndrome differentiation and treatment of diabetic peripheral neuropathy and effect of Huangqi Guizhi Wuwu decoction on PI3K/AKT and oxidative stress of Schwann cells in high glucose environment [Master’s thesis]. Ningxia Med Univ.

 Google Scholar

Zhang K, Peng P, Huang J, Chen M, Liu F, Zhu C, Lu Q, Wang M, Lin C. 2024. Integrating plasma metabolomics and gut microbiome to reveal the mechanisms of Huangqi Guizhi Wuwu decoction intervene diabetic peripheral neuropathy. J Ethnopharmacol. 319(Pt 3):117301. doi:10.1016/j.jep.2023.117301.

 PubMedGoogle Scholar

Zhang Y, Long H, Wang X, Cao W, Wu L, Liu T, Zhou J. 2023a. Effect of Huangqi Guizhi Wuwu decoction on apoptosis-related bax and caspase-12 of sciatic nerve cells in diabetic rats. Chin J Experimental Tradi Med Formulae. 29:58–64. Chinese.

 Google Scholar

Zhang Y, Long H, Wang X, Cao W, Wu L, Liu T, Zhou J. 2023b. Effect of Huangqi Guizhi Wuwu decoction on IRE1α/CHOP pathway of endoplasmic reticulum stress in sciatic nerve of diabetic rats. Chin J Experimental Tradi Med Formulae. 29:43–51. Chinese.

 Google Scholar

Cheng S, Zhou X, Li X, Wu D, Qian T, Zhang W. 2019. Based on NF-κB signaling pathway, explore the protective mechanism of Danggui Sini decoction on peripheral neuropathy in diabetic rats. J Changchun Univ Chinese Med. 35:128–131. Chinese.

 Google Scholar

He Y, Huang Y, Guan H, Wang X, Luo J, JW, Shi Y. 2019. Effect and mechanism of compound Longqi decoction on peripheral neuropathy in type 2 diabetic rats. Chin Archi Tradit Chin Med. 37:2694–2698. Chinese.

 Google Scholar

Wei M, Tian Y, Huang D, Zhu X, Feng C, Wang H, Li M. 2019. Effect of Tangtongfang on the expression of PARP and NF-κB in sciatic nerve of rats with diabetic peripheral neuropathy. Chin Archi Tradit Chin Med. 37:1844–1848. Chinese.

 Google Scholar

He H. 2021. Study on the mechanism of Tangtong recipe regulating autophagy in the treatment of diabetic peripheral neuropathy [Master’s thesis]. Chin Academy Chinese Med Sciences.

 Google Scholar

Zhang L, Qi Y, Zhang L. 2022. Based on Sirt1/PGC1α/TFAM pathway, the mechanism of Yiqi Huoxue Tongluo recipe in treating diabetic peripheral neuropathy was discussed. Chin J Tradit Chinese Med Pharm. 37:5395–5399. Chinese.

 Google Scholar

Liu G, Zhang Y, Qin L, Zhang C, Zhang Q, Bai H, Zhao Y, Liu T, Mu X. 2023. Tangbikang granules regulates the AMPK/PGC-1α/SIRT3 signal pathway and inhibits oxidative stress of sciatic nerve in diabetic rats. Chin J Experimental Tradi Med Formulae. 30:75–82. Chinese.

 Google Scholar

Yu MX, Lei B, Song X, Huang YM, Ma XQ, Hao CX, Yang WH, Pan ML. 2021. Compound Xiongshao capsule ameliorates streptozotocin-induced diabetic peripheral neuropathy in rats via inhibiting apoptosis, oxidative-nitrosative stress and advanced glycation end products. J Ethnopharmacol. 268:113560. doi:10.1016/j.jep.2020.113560.

 PubMed Web of Science ®Google Scholar

Hu Y, Chen C, Liang Z, Liu T, Hu X, Wang G, Hu J, Xie X, Liu Z. 2023. Compound Qiying Granules alleviates diabetic peripheral neuropathy by inhibiting endoplasmic reticulum stress and apoptosis. Mol Med. 29(1):98. doi:10.1186/s10020-023-00698-3.

 PubMed Web of Science ®Google Scholar

Liu Q. 2021. Target-effect metabonomics study of Liuwei Luobi granule in improving diabetic peripheral neuropathy in db/db mice [dissertation]. Chin Academy Chinese Med Sciences.

 Google Scholar

Wang Y, Huang X, Feng M. 2023. Effects of Chaihu Shugan powder on transient receptor potential vanillin Subtype 1/Calcitonin Gene Related peptide pathway and electrophysiological changes of sciatic nerve in diabetic peripheral neuropathy rats. Anhui Med Pharm J. 27:1312–1317 + 1485. Chinese.

 Google Scholar

Liu M. 2020. Clinical observation of Qiguitangtongning granule on patients with type 2 diabetic peripheral neuropathy and its influence on the expression of perk and chop in model rats [Master’s thesis]. Anhui Univ Chinese Med.

 Google Scholar

Cao B. 2018. Clinical observation on Danggui Sini decoction in treating diabetic peripheral neuropathy of cold coagulation and blood stasis type. Guide China Med. 16:188–189. Chinese.

 Google Scholar

Yang H. 2017a. Effect of Danggui Sini decoction on hemorheology and nerve conduction velocity in elderly diabetic peripheral neuropathy with blood deficiency and cold coagulation. Modern J Integrated Tradit Chinese Western Med. 26:1755–1757. Chinese.

 Google Scholar

Chen X. 2018. Clinical study on Danggui Sini decoction in treating diabetic peripheral neuropathy with cold-dampness and spleen-trapped type. Chinese Med Nat Prod. 33:756–759. Chinese.

 Google Scholar

Lu Q, Chen B, Liang Q, Wu L, Luo L, Li A, Ouyang W, Wen Z, Liu Y, Lu J, et al. 2022. Xiaoketongbi formula vs. pregabalin for painful diabetic neuropathy: a single-center, randomized, single-blind, double-dummy, and parallel controlled clinical trial. J Diabetes. 14(8):551–561. doi:10.1111/1753-0407.13306.

 PubMed Web of Science ®Google Scholar

Zhang X, Dong H, Feng J, Cui L, Guo F, Zhao L, Li Y, Su R. 2019. Effect of Wenyang Tongluo collaterals on the expression of serum nerve growth factor in diabetic peripheral neuropathy. Chinese Remedies Clinics. 19:739–740. Chinese.

 Google Scholar

Cheng D, Xia H, Huang F. 2020. Clinical observation on treatment of diabetic peripheral neuropathy with traditional Chinese medicine decoction. Chin Continuing Med Edu. 12:161–163. Chinese.

 Google Scholar

Chen D, Zhang Y. 2023. Clinical effect of tangmanning decoction combined with lipoic acid on diabetic peripheral neuropathy. Chinese J Clin Rational Drug Use. 16:82–85. Chinese.

 Google Scholar

Zhang H. 2020. Clinical evaluation of tangmanning, a compound preparation of traditional Chinese medicine, in the treatment of diabetic peripheral neuropathy. Guide Chin Med. 18:130–131. Chinese.

 Google Scholar

Shi H. 2019. Clinical effect of Huangqi Danshen Tongluo recipe on diabetic peripheral neuropathy. Clin Res Prac. 4:114–115. Chinese.

 Google Scholar

Li M. 2021. Clinical effect of Buyanghuanwu decoction on diabetic peripheral neuropathy with qi deficiency and blood stasis. Chin Health Standard Manage. 12:127–129. Chinese.

 Google Scholar

Zhou P, Xie W, Meng X, Zhai Y, Dong X, Zhang X, Sun G, Sun X. 2019. Notoginsenoside R1 ameliorates diabetic retinopathy through PINK1-dependent activation of mitophagy. Cells. 8(3):213. doi:10.3390/cells8030213.

 PubMed Web of Science ®Google Scholar

Yang X, Zhang L, Li T, Sheng L, Guo W. 2019. Clinical efficacy of Qiteng Tongluo decoction in the treatment of type 2 diabetic peripheral neuropathy. Chin J Integrative Med Cardio-Cerebrovasc Dis. 17:4069–4072. Chinese.

 Google Scholar

Zhang Y, Zhang M. 2018. Clinical effect of Fuyuan Huoxue decoction on diabetic peripheral neuropathy. World Latest Med Inf. 18:161. Chinese.

 Google Scholar

Zhang H. 2018. Clinical  effect  of  Fuyuan  Huoxue  decoction  on  diabetic  peripheral  neuropathy. World  Latest  Med Inf. 18:131–137. Chinese.

 Google Scholar

Zhou Y. 2017. Study on the clinical effect of Chinese medicine for warming yang, activating blood circulation and dredging collaterals on diabetic peripheral neuropathy. Guide Chin Med. 15:192. Chinese.

 Google Scholar

Yang L. 2017b. Clinical observation on 100 cases of diabetic peripheral neuropathy treated with Chinese medicine of supplementing qi and promoting blood circulation. Guide Chin Med. 15:205–206. Chinese.

 Google Scholar

Wang H, Lu B. 2017. Treatment of 80 cases of diabetic peripheral neuropathy with Qidan Dihuang decoction. World Latest Med Inf. 17:129. Chinese.

 Google Scholar

Peng X, Liang B, Song R, Wang H, Chen L, Hou J, Liu J, Ren L, Yuan Q. 2023. Effect of modified Taohong Siwu decoction on diabetic peripheral neuropathy. Jilin J Tradit Chinese Med. 43:170–173. Chinese.

 Google Scholar

Wu J, Fu Y, Wu YX, Wu ZX, Wang ZH, Li P. 2021. Lycorine ameliorates isoproterenol-induced cardiac dysfunction mainly via inhibiting inflammation, fibrosis, oxidative stress and apoptosis. Bioengineered. 12(1):5583–5594. doi:10.1080/21655979.2021.1967019.

 PubMed Web of Science ®Google Scholar

Mu C. 2016. Analysis of therapeutic effect of Jiangtang Tongmailing capsule on diabetic peripheral neuropathy. Heilongjiang J Tradit Chinese Med. 45:13–14. Chinese.

 Google Scholar

Wen Y. 2017. Clinical analysis of Danshen Gegen formula granule in treating diabetic peripheral neuropathy. Electronic J Clin Med Literature. 4:5887–5890. Chinese.

 Google Scholar

Cui H, Zhu W, Zhou J, Xiao Q, Huang J, Shen X, Yang W. 2018. Clinical observation on treatment of diabetic peripheral neuropathy with compound Xiongshao capsule. Chin Pharm. 29:223–228.

 Google Scholar

Wu Q, Yan G, Zeng D, Zhang M, Li L, Lu J. 2019. Clinical observation on 30 cases of diabetic peripheral neuropathy treated by Jiangtang Huoluo pill combined with fumigation and washing with traditional Chinese medicine. Hunan J Tradit Chinese Med. 35:1–3 + 11. Chinese.

 Google Scholar

Data availability statement

The data are available from the corresponding author upon reasonable request.