Comparative Efficacy of East Asian Herbal Formulae Containing Astragali Radix–Cinnamomi Ramulus Herb-Pair against Diabetic Peripheral Neuropathy and Mechanism Prediction: A Bayesian Network Meta-Analysis Integrated with Network Pharmacology
Abstract
:1. Introduction
2. Materials and Methods
2.1. Search Strategy
2.2. Study Selection
2.2.1. Type of Studies
2.2.2. Type of Participants
2.2.3. Type of Interventions
2.2.4. Type of Outcome Measures
2.3. Data Extraction
2.4. Methodological Quality Assessment
2.5. Data Analysis
2.5.1. Pairwise Meta-Analysis
2.5.2. Network Meta-Analysis
2.5.3. Network Pharmacology Analysis of the Synergistic Mechanism of the ACP against DPN
3. Results
3.1. Study Identification
3.2. Study Characteristics
3.3. Risk of Bias
Included Study (Reference) | Type of Diabetes/Diagnosis Criteria | Trial Design/Randomization Method | Number of Participants (Male/Female); Age (Mean ± SD) | Interventions | Morbidity Period (Mean ± SD or Range) | Outcome Index (Intergroup Differencies p-Value) | Course of Treatment | Adverse Event (Case/Symptom) | |||
---|---|---|---|---|---|---|---|---|---|---|---|
Trial | Control | Trial | Control | Trial | Control | ||||||
Jin 2004 [59] | T1DM and T2DM/ WHO criteria, 1999 | Randomized; Single center; Parallel/NR | 103 (54/49) 59.4 ± 5.61 y | 99 (51/48) 58.81 ± 6.01 y | Tangmaitong tablets (0.5 g × 4 t, t.i.d.) | Mecobalamin tablets (500 mg, t.i.d.) | 3.31 ± 1.25 y | 3.82 ± 1.17 y | 1. MMNCV (p > 0.05) 2. MSNCV (p < 0.01) 3. PMNCV (p < 0.05) 4. PSNCV (p < 0.01) | 8 w | Trial: 1 AE/diarrhea Control: 3 AEs/abdomnial pain with diarrhea |
Sun 2008 [60] | T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/NR | 30 (18/12) 40~70 y | 30 (16/14) 43~69 y | 1. Ziyinbushenhuoxuetonglou fang decoction (300 mL, b.i.d.) 2. Mecobalamin tablets (500 mg, t.i.d.) | Mecobalamin tablets (500 mg, t.i.d.) | 1~33 m | 1~34 m | 1. Response rate (p < 0.05) | 4 w | NR |
Shen 2009 [61] | T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/Block randomization method | 50 (21/29) 60 ± 4.2 y | 50 (27/23) 58.81 ± 6.01 y | Tangmaining capsule (4.5 g × 5 c, b.i.d.) | Mecobalamin tablets (500 mg, t.i.d.) | 8.5 y | 7.9 y | 1. Response rate (p < 0.05) 2. MMNCV (p < 0.05) 3. MSNCV (p < 0.05) 4. UMNCV (p < 0.01) 5. USNCV (p < 0.01) 6. PMNCV (p < 0.05) 7. PSNCV (p > 0.05) 8. TMNCV (p > 0.05) 9. TSNCV (p < 0.01) | 8 w | Trial: No AE Control: No AE |
Lin 2010 [62] | T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/NR | 40 (22/18) median 55.6 y | 40 (23/19) median 54.2 y | 1. Tongxinluo capsule (3c, t.i.d.) 2. Mecobalamin tablets (500 mg, t.i.d.) | Mecobalamin tablets (500 mg, t.i.d.) | NR | NR | 1. Response rate (p < 0.05) 2. PMNCV (p < 0.01) 3. PSNCV (p < 0.01) 4. TMNCV (p < 0.01) 5. TSNCV (p < 0.01) | 4 w | NR |
Wang 2010 [63] | T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/Simple randomization using random number table | 80 (45/35) 62.68 ± 7.35 y | 79 (43/36) 62.78 ± 7.57 y | 1. Huangqiguizhiwuwu decoction (300 mL, b.i.d.) 2. Mecobalamin injection (0.5 mg, q.d., i.m.) | Mecobalamin injection (0.5 mg, q.d., i.m.) | 7.12 ± 4.25 y | 6.98 ± 4.62 y | 1. Response rate (p < 0.01) 2. MMNCV (p < 0.01) 3. MNSCV (p < 0.01) 4. PMNCV (p < 0.01) 5. PSNCV (p < 0.01) | 12 w | NR |
Yan 2010 [64] | T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/NR | 14 (7/7) 57.79 ± 6.73 y | 15 (6/9) 52.53 ± 8.0 y | Shutangluofang granule (b.i.d.) | Methylcobalamine (500 mg, t.i.d.) | 13.14 ± 10.58 m | 10.67 ± 11.14 m | 1. Response rate (p < 0.05) | 12 w | NR |
Wu 2011 [65] | T1DM and T2DM/Guidelines for the Prevention and Treatment of Diabetes in China, 2004 | Randomized; Single center; Parallel/NR | 30 (16/14) mean 49.9 y | 27 (15/12) mean 48 y | Modified yiqihuoxue decoction (300 mL, b.i.d.) | Vitamin B1 (20 mg, t.i.d.) Vitamin B6 (20 mg, t.i.d.) | mean 12 m | mean 11.4 m | 1. Response rate (p < 0.01) 2. PMNCV (p < 0.01) 3. PSNCV (p < 0.01) | 6 w | NR |
Gao 2012 [66] | T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/NR | 30 (16/14) NR | 30 (17/13) NR | 1. Nourishing the liver to stop the wind and tongluo decoction 2. Methylcobalamine (0.5 mg, t.i.d.) | Methylcobalamine (0.5 mg, t.i.d.) | NR | NR | 1. Response rate (p < 0.05) 2. MMNCV (p < 0.01) 3. MSNCV (p < 0.01) 4. PMNCV (p < 0.01) 5. PSNCV (p < 0.01) | 8 w | Trial: 2 AEs/ nausea, upper abdominal discomfort Control: No AE |
Gong 2013 [67] | T1DM and T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/NR | 60 (32/28) 56.42 ± 5.28 y | 60 (33/27) 57.16 ± 5.34 y | 1. Modified aconiti decoction (400 mL, b.i.d.) 2. Methylcobalamine (500 mg, t.i.d.) | Methylcobalamine (500 mg t.i.d.) | 7.65 ± 3.84 m | 7.83 ± 3.29 m | 1. Response rate (p < 0.05) 2. PMNCV (p < 0.01) 3. PSNCV (p > 0.05) | 30 d | Trial: No AE Control: No AE |
Han 2013 [68] | T1DM and T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/Simple randomization using random number table | 31 (17/14) 54.2 ± 9.6 y | 31 (16/15) 55.3 ± 10.1 y | 1. Modified huangqiguizhiwuwu decoction (400 mL, b.i.d.) 2. Methylcobalamine (0.5 mg, t.i.d.) | Methylcobalamine (0.5 mg, t.i.d.) | NR | NR | 1. Response rate (p < 0.05) 2. PMNCV (p < 0.01) 3. PSNCV (p < 0.01) 4. MMNCV (p < 0.01) 5. MSNCV (p < 0.01) | 8 w | NR |
Zhang 2013a [69] | T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/NR | 30 (16/14) 54.32 ± 7.14 y | 30 (15/15) 56.24 ± 7.40 y | 1. Mudan tong luo fang (b.i.d.) 2. α-Lipoic acid injection (600 mg, q.d., i.v. drip) | α-Lipoic acid injection (600 mg, q.d., i.v. drip) | 8.3 ± 1.67 y | 8.5 ± 1.54 y | 1. Response rate (p < 0.05) 2. MMNCV (p < 0.05) 3. MSNCV (p < 0.05) 4. PMNCV (p < 0.05) 5. PSNCV (p < 0.05) | 3 w | NR |
Zhang 2013b [70] | T1DM and T2DM/Only diagnostic criteria are presented without reference. | Randomized; Single center; Parallel/NR | 30 Total 60 (36/14) 56 ± 8 y | 30 Total 60 (36/14) 56 ± 8 y | Tang bao kang (20 pills, t.i.d.) | 1. Methylcobalamine (500 mg, t.i.d.) 2. Vitamin B1 (30 mg, t.i.d.) 3. Vitamin B6 (30 mg, t.i.d.) | Total 5~10 y | Total 5~10 y | 1. Response rate (p < 0.01) 2. MMNCV (p < 0.01) 3. MSNCV (p < 0.01) 4. UMNCV (p < 0.01) 5. USNCV (p < 0.01) 6. PMNCV (p < 0.01) 7. PSNCV (p < 0.01) | 24 w | Trial: No AE Control: 1 AE/skin rash |
Guo 2014 [71] | T1DM and T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/NR | 32 (19/13) 64.78 ± 8.90 y | 32 (15/17) 65.59 ± 8.35 y | 1. Modified huangqiguizhiwuwu decoction (b.i.d.) 2. Mecobalamin tablets (0.5 mg, t.i.d.) 3. Gabapentin (600 mg, t.i.d.) | 1. Mecobalamin tablets (0.5 mg, t.i.d.) 2. Gabapentin (600 mg, t.i.d.) | NR | NR | 1. Response rate (p < 0.01) | 8 w | NR |
Yang 2014a [73] | T2DM/Diagnostic criteria of Chinese guidelines for the prevention and treatment of type 2 diabetes, 2008 | Randomized; Single center; Parallel/NR | 60 (35/25) 51.30 ± 6.03 y | 60 (37/23) 51.26 ± 5.38 y | 1. Shenqixuebi feng (b.i.d.) 2. α-Lipoic acid injection (0.3 g, q.d., i.v. drip) 3. Mecobalamin injection (0.5 mg, q.d., i.v. drip) | 1. α-Lipoic acid injection (0.3 g, q.d., i.v. drip) 2. Mecobalamin injection (0.5 mg, q.d., i.v. drip) | 3.65 ± 1.12 y | 3.36 ± 1.18 y | 1. Response rate (p < 0.05) | 4 w | NR |
Yang 2014b [72] | T1DM and T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/NR | 36 (23/13) 47.8 ± 8.3 y | 36 (20/16) 46.5 ± 8.1 y | 1. Modified huangqiguizhiwuwu decoction (200 mL, q.d.) 2. Methylcobalamine injection (500 mg, q.d., i.m.) | 1. Methylcobalamine injection (500 mg, q.d., i.m.) | 4.1 ± 1.3 m | 3.9 ± 1.4 m | 1. Response rate (p < 0.05) | 4 w | NR |
Qi 2015 [74] | T1DM and T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/NR | 32 (17/15) 53.2 ± 7.1 y | 32 (16/16) 52.4 ± 7.0 y | 1. Mudan granule (7 g, t.i.d.) 2. 0.9% Sodium chloride 200 mL + α-Lipoic acid injection (450 mg, q.d., i.v. drip) | 1. 0.9% Sodium chloride 200 mL + α-Lipoic acid injection (450 mg, q.d., i.v. drip) | 2.3 ± 2.1 y | 2.6 ± 1.9 y | 1. Response rate (p < 0.05) 2. PMNCV (p < 0.01) 3. PSNCV (p < 0.01) | 4 w | Trial: No AE Control: No AE |
Wang 2015 [75] | T2DM/TCM diagnosis and treatment plan for 95 diseases in 22 specialties | Randomized; Single center; Parallel/NR | 40 (20/20) mean 68.5 y | 40 (23/17) mean 71.2 y | 1. Yinxinshu capsule (3c, t.i.d.) 2. Maixuekang capsule (3c, t.i.d.) | 1. Oryzanol (20 mg, t.i.d.) 2. Vitamin B1 (10 mg, t.i.d.) 3. Adenosylcobalamin (1 mg, t.i.d.) | 10~12 y | 10~12 y | 1. Response rate (p < 0.05) | 4 w | Trial: No AE Control: No AE |
Xue 2015 [76] | T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/Simple randomization using random number table | 42 (23/19) 36~78 y | 42 (22/20) 35~78 y | 1. Modified liutengshuilushexian decoction (150 mL, q.d.) | 1. Methylcobalamine tablet (0.5 mg, t.i.d.) | 28~73 d | 30~73 d | 1. Response rate (p < 0.01) 2. MSNCV (p < 0.01) 3. TSNCV (p < 0.01) 4. PSNCV (p < 0.01) | 3 w | Trial: No AE Control: No AE |
Guo 2016 [77] | T1DM and T2DM/Diabetic peripheral neuropathy diagnosis and treatment guidelines of China, 2009 | Randomized; Single center; Parallel/Simple randomization using random number table | 51 (26/25) 69.54 ± 5.06 y | 51 (28/23) 69.78 ± 5.96 y | 1. Qitengtongluo decoction (b.i.d.) 2. Epalrestat (50 mg, 1t, t.i.d.) | 1. Epalrestat (50 mg, 1 t, t.i.d.) | 1.91 ± 2.09 y | 6.59 ± 1.91 y | 1. Response rate (p < 0.05) 2. NCSS (p < 0.05) 3. MSNCV (p < 0.05) 4. TSNCV (p < 0.05) 5. PMNCV (p < 0.05) 6. PSNCV (p < 0.05) | 12 w | NR |
Han 2016 [78] | TIDM and T2DM/Diagnostic criteria for diabetic peripheral neuropathy formulated by the Chinese Medical Doctor Association | Randomized; Single center; Parallel/NR | 20 (12/8) 54.3 ± 7.2 y | 20 (11/9) 53.7 ± 6.8 y | 1. Zhanjin tongluo Chinese medicine (b.i.d.) 2. Mecobalamin tablets (500 mg, t.i.d.) | 1. Mecobalamin tablets (500 mg, t.i.d.) | 2.4 ± 1.2 y | 2.6 ± 1.3 y | 1. Response rate (p < 0.05) | 4 w | NR |
Lan 2016 [79] | T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/NR | 54 Other information NR | 54 Other information NR | Yiqihuoxue tongluo capsule (1.2 g, t.i.d.) | Epalrestat tablets (50 mg, t.i.d.) | NR | NR | 1. Response rate (p < 0.05) 2. PMNCV (p < 0.05) | 12 w | Trial: No AE Control: No AE |
Mo 2016 [82] | T2DM/Guidelines for the Prevention and Treatment of Type 2 Diabetes in China, 2013 | Randomized; Single center; Parallel/Simple randomization using random number table | 33 (19/14) 65.28 ± 9.098 y | 32 (17/15) 62.34 ± 8.168 y | Yangyinjiedu decoction (300 mL, b.i.d.) | Methylcobalamine (0.5 mg t.i.d.) | 2~23 y | 2~19 y | 1. Response rate (p < 0.01) | 8 w | NR |
Wang 2016 [83] | T2DM/Guidelines for the Prevention and Treatment of Type 2 Diabetes in China, 2013 | Randomized; Single center; Parallel/Simple randomization using random number table | 124 (72/52) 57.3 ± 6.8 y | 103 (58/45) 58.1 ± 7.2 y | Modified tangbitong feng (150 mL, b.i.d.) | Lifestyle modification | 22.1 ± 5.4 m | 23.5 ± 4.8 m | 1. Response rate (p < 0.01) | 8 w | Trial: No AE Control: No AE |
Li 2016a [80] | T1DM and T2DM/Diabetic peripheral neuropathy diagnosis and treatment of China, 2009 | Randomized; Single center; Parallel/Simple randomization using random number table | 30 (18/12) 49.6 ± 5.6 y | 30 (17/13) 50.3 ± 5.4 y | 1. Wenyanghuoxuetongbi feng (b.i.d.) 2. Methylcobalamine (0.5 mg, t.i.d.) | 1. Methylcobalamine (0.5 mg, t.i.d.) | 18.21 ± 12.37 m | 17.97 ± 12.54 m | 1. Response rate (p < 0.01) 2. TSNCV (p < 0.01) 3. PSNCV (p < 0.05) | 8 w | Trial: No AE Control: No AE |
Zhang 2016a [85] | T1DM and T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/Simple randomization using random number table | 48 (26/22) 54.6 y | 48 (28/20) 55.2 y | 1. Huangichifeng decoction combined Dangguisini decoction (q.d.) 2. Methylcobalamine injection (500 mg, q.d., i.m.) | 1. Methylcobalamine injection (500 mg, q.d., i.v.) | 2.8 y | 3.2 y | 1. Response rate (p < 0.01) 2. MSNCV (p < 0.01) 3. USNCV (p < 0.01) 4. PMNCV (p < 0.01) 5. TMNCV (p < 0.01) | 4 w | NR |
Li 2016b [81] | T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/NR | 60 (37/23) 57 y | 60 (35/25) 56 y | Huangzhitongnaoluo capsule (3c, t.i.d.) | Mecobalamin dispersible tablets (500 mg, t.i.d.) | 1~13 y | 1~12 y | 1. Response rate (p < 0.05) 2. MSNCV (p < 0.05) 3. TMNCV (p < 0.05) | 12 w | NR |
Zhang 2016b [84] | T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/Simple randomization using random number table | 60 (36/24) 55.3 ± 6.4 y | 60 (35/25) 55.6 ± 5.5 y | 1. Qiming granule (4.5 g, t.i.d.) 2. Nimodipine injection (8 mg, q.d., i.v. drip) | 1. Nimodipine injection (8 mg, q.d., i.v. drip) | 2.0 ± 1.1 y | 2.2 ± 1.0 y | 1. Response rate (p < 0.01) 2. MMNCV (p < 0.01) 3. MSNCV (p < 0.01) 4. UMNCV (p < 0.05) 5. USNCV (p < 0.01) 6. TMNCV (p < 0.05) 7. TSNCV (p < 0.01) | 12 w | Trial: No AE Control: 1 AE/mild dizziness |
Chen 2017 [86] | T2DM/Guidelines for the Prevention and Treatment of Type 2 Diabetes in China, 2013 | Randomized; Single center; Parallel/Simple randomization using random number table | 30 (14/16) 38.72 ± 20.02 y | 30 (13/17) 39.11 ± 19.57 y | Dagguisini decoction (300 mL, b.i.d.) | Epalrestat capsule (50 mg, t.i.d.) | 4.32 ± 2.05 y | 4.20 ± 2.01 y | 1. Response rate (p < 0.05) | 12 w | Trial: No AE Control: No AE |
Shi 2017 [87] | T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/NR | 32 (20/12) 38.7 ± 8.1 y | 32 (22/10) 40.3 ± 10.1 y | 1. Fufang danshen dripping pill (10 pill, t.i.d.) | 1. Methylcobalamine (0.5 mg, t.i.d.) 2. Epalrestat (50 mg, t.i.d.) | 3.87 ± 1.5 y | 3.69 ± 1.3 y | 1. TSNCV (p < 0.01) | 15 w | NR |
Wang 2017 [88] | T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/Simple randomization using random number table | 30 (15/15) 58.76 ± 4.32 y | 30 (16/14) 57.21 ± 3.56 y | Dangguisini decoction (200 mL, b.i.d.) | Mecobalamin tablets (500 mg, t.i.d.) | 3.56 ± 1.21 y | 3.84 ± 1.36 y | 1. Response rate (p < 0.05) 2. MMNCV (p > 0.05) 3. MSNCV (p > 0.05) 4. PMNCV (p < 0.05) 5. PSNCV (p < 0.05) 6. TMNCV (p < 0.05) 7. TSNCV (p < 0.05) | 8 w | NR |
Chen 2018 [89] | T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/Simple randomization using random number table | 40 (19/21) 55.8 ± 4.7 y | 40 (20/20) 56.2 ± 2.8 y | 1. Dangguisinin decoction (b.i.d.) 2. Mecobalamin tablets (500 mg, t.i.d.) | Mecobalamin tablets (500 mg, t.i.d.) | 3.6 ± 1.8 y | 2.4 ± 2.1 y | 1. Response rate (p < 0.05) | 4 w | Trial: 2 AEs/skin rash, gastrointestinal discomfort Control: 3 AEs/diarrhea (2), skin rash |
Dai 2018 [90] | T2DM/Guidelines for the Prevention and Treatment of Type 2 Diabetes in China, 2013 | Randomized; Single center; Parallel/NR | 40 45~85 y Other information NR | 40 45~85 y Other information NR | Modified huangqiguizhiwuwu decoction (500 mL, b.i.d.) | Epalrestat capsule (50 mg, t.i.d.) | NR | NR | 1. Response rate (p < 0.05) 2. UMNCV (p < 0.05) 3. USNCV (p < 0.05) 4. PMNCV (p < 0.05) 5. PSNCV (p < 0.05) | 3 w | NR |
Hu 2018 [92] | T2DM/Guidelines for the Prevention and Treatment of Type 2 Diabetes in China, 2013 | Randomized; Single center; Parallel/NR | 31 (13/18) 55.45 ± 11.52 y | 31 (15/16) 53.76 ± 2.03 y | 1. Modified jiajianhuangqiguizhiwuwu decoction (200 mL, b.i.d.) 2. Methylcobalamine (0.5 mg, t.i.d.) | 1. Methylcobalamine tablet (0.5 mg, t.i.d.) | 7.13 ± 2.01 y | 6.52 ± 1.95 y | 1. Response rate (p < 0.05) 2. PMNCV (p < 0.05) | 8 w | NR |
Huang 2018 [93] | T1DM and T2DM/Diagnostic and therapeutic effect evaluation criteria of diseases and syndromes in traditional Chinese medicine, 1994 | Randomized; Single center; Parallel/Simple randomization using random number table | 120 (52/68) 51.3 ± 11.4 y | 120 (51/69) 50.9 ± 11.6 y | Matong powder (7 g, t.i.d.) | Methylcobalamine tablet (0.5 mg, t.i.d.) | 8.92 ± 8.6 m | 8.97 ± 8.5 m | 1. Response rate (p < 0.05) 2. PMNCV (p < 0.05) 3. TSNCV (p < 0.05) | 8 w | Trial: 3 AEs/ Abdominal bloating with anorexia (3) Control: 2 AEs/Abdominal bloating with anorexia (2) |
She 2018 [94] | T2DM/Guidelines for the Prevention and Treatment of Type 2 Diabetes in China, 2010 | Randomized; Single center; Parallel/Simple randomization using random number table | 30 (18/12) 63.35 ± 7.12 y | 30 (17/13) 65.13 ± 6.21 y | 1. Huangqiguizhiwuwu granule (b.i.d.) 2. Mecobalamin tablet (1 mg, t.i.d.) | Mecobalamin tablet (1 mg, t.i.d.) | 3.31 ± 2.06 y | 3.82 ± 1.97 y | 1. Response rate (p < 0.05) | 6 w | NR |
Xin 2018 [95] | T2DM/Diabetic peripheral neuropathy diagnosis and treatment of China, 2009 | Randomized; Single center; Parallel/NR | 30 Total 60 (36/24) 55.3 y | 30 Total 60 (36/24) 55.3 y | 1. Mongolian medicine garidi-13 weiwan (3 g, q.d.) | Mecobalamin tablet (0.5 mg, t.i.d.) | Total 4.2 y | Total 4.2 y | 1. Response rate (p < 0.05) | 4 w | NR |
Gao 2019 [91] | T1DM and T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/NR | 50 (26/24) 60.83 ± 5.26 y | 50 (25/25) 61.17 ± 6.05 y | 1. Modified shegmaisan (300 mL, b.i.d.) 2. Mecobalmin tablet (500 mg, t.i.d.) | Mecobalmin tablet (500 mg, t.i.d.) | 3.82 ± 1.04 y | 3.77 ± 1.12 y | 1. Response rate (p < 0.05) 2. MMNCV (p > 0.05) 3. MSNCV (p > 0.05) 4. PMNCV (p < 0.05) 5. PSNCV (p < 0.05) 6. TMNCV (p < 0.05) 7. TSNCV (p < 0.05) | 8 w | Trial: No AE Control: No AE |
Wu 2019 [99] | T2DM/Guidelines for the Prevention and Treatment of Type 2 Diabetes in China, 2013 | Randomized; Single center; Parallel/Simple randomization using random number table | 30 (16/14) 57.60 ± 7.20 y | 30 (16/14) 57.03 ± 7.63 y | Taohongsiwu decoction (t.i.d.) | Epalrestat tablet (50 mg, t.i.d.) | 4.3 y | 4.3 y | 1. Response rate (p < 0.05) 2. MSNCV (p < 0.05) 3. PSNCV (p < 0.05) | 4 w | Trial: No AE Control: No AE |
Yi 2019 [100] | T1DM and T2DM/Diabetic neuropathy diagnosis criteria of American Diabetes Association, 2017 | Randomized; Single center; Parallel/Simple randomization using random number table | 60 (31/29) 61.36 ± 4.37 y | 60 (29/31) 61.53 ± 4.64 y | Mongolian medicine zhenbo pills (0.2 g × 15 p, b.i.d.) | α-Lipoic acid tablet (0.3 g × 2 c, q.d.) | 8.23 ± 3.21 y | 8.23 ± 3.12 y | 1. MMNCV (p < 0.05) 2. MSNCV (p < 0.05) 3. PMNCV (p < 0.05) 4. PSNCV (p < 0.05) | 24 w | Trial: 5 AEs/ nausea (2), anorexia (3) Control: 6 AEs/ nausea (2), gastric pain (2) |
Ji 2019 [96] | T2DM/Guidelines for the Prevention and Treatment of Type 2 Diabetes in China, 2010 | Randomized; Single center; Parallel/Simple randomization using random number table | 54 (32/22) 54.47 ± 9.81 y | 53 (33/20) 54.81 ± 9.44 y | 1. Yangyinzhuyu decoction (150 mL, b.i.d.) 2. Epalrestat tablet (50 mg, t.i.d.) | Epalrestat tablet (50 mg, t.i.d.) | 10.24 ± 3.08 y | 10.53 ± 2.66 y | 1. Response rate (p < 0.05) | 90 d | Trial: No AE Control: No AE |
Liu 2019a [97] | T2DM/Guidelines for the Prevention and Treatment of Type 2 Diabetes in China, 2013 | Randomized; Single center; Parallel/Simple randomization using random number table | 40 Other information NR | 40 Other information NR | 1. Shengjinsan combined Taohongyin (200 mL, b.i.d.) 2. Mecobalamin tablet (500 mg, t.i.d.) | Mecobalamin tablet (500 mg, t.i.d.) | NR | NR | 1. MMNCV (p < 0.05) 2. MSNCV (p < 0.05) 3. TMNCV (p < 0.05) 4. TSNCV (p < 0.05) | 4 w | NR |
Liu 2019b [98] | T2DM/Guidelines for the Prevention and Treatment of Type 2 Diabetes in China, 2013 | Randomized; Single center; Parallel/Simple randomization | 45 (27/18) 58.77 ± 4.26 y | 45 (26/19) 59.46 ± 4.77 y | 1. Huangqiguizhiwuwu decoction (400 mL, b.i.d.) 2. Epalrestat tablets (t.i.d.) 3. Mecobalamin tablet (t.i.d.) | 1. Epalrestat tablets (t.i.d.) 2. Mecobalamin tablet (t.i.d.) | 3.28 ± 1.45 m | 3.31 ± 1.13 m | 1. Response rate (p < 0.05) | 8 w | NR |
Chen 2021 [101] | T2DM/Guidelines for the Prevention and Treatment of Type 2 Diabetes in China, 2013 | Randomized; Single center; Parallel/NR | 28 (15/13) 57.2 ± 8.1 y | 29 (16/13) 56.5 ± 7.6 y | 1. Zicuijuanbi decoction (150 mL, b.i.d.) 2. Normal saline injection (250 mL, i.v.) | 1. gabapentin capsule (0.3 g, t.i.d.) 2. Normal saline injection (250 mL, i.v.) | 15.57 ± 3.68 y | 14.59 ± 4.35 y | 1. Response rate (p < 0.05) | 10 w | NR |
Hou 2021 [102] | T2DM/WHO criteria, 1999 | Randomized; Single center; Parallel/NR | 39 (24/15) 56.74 ± 11.79 y | 28 (18/10) 55.83 ± 10.60 y | Jiuchongdan (40 pills, t.i.d.) | Mecobalamin tablet (500 mg, t.i.d.) | 15.28 ± 11.23 m | 16.72 ± 10.96 m | 1. Response rate (p < 0.05) 2. PSNCV (p < 0.05) 3. MSNCV (p < 0.05) 4. USNCV (p < 0.05) | 12 w | NR |
Li 2021 [103] | T2DM/Guidelines for the Prevention and Treatment of Diabetic Peripheral Neuropathy by Traditional Chinese Medicine, 2011 | Randomized; Single center; Parallel/Simple randomization using random number table | 41 (22/19) 59.81 ± 5.63 y | 41 (23/18) 60.20 ± 5.62 y | 1. Huangqiguizhiwuwu decoction (200 mL, t.i.d.) combined Mudan granule (7 g, t.i.d.) 2. Mecobalmin tablet (500 mg, t.i.d.) | 1. Mecobalamin tablet (500 mg, t.i.d.) | 3.15 ± 0.45 y | 3.12 ± 0.43 y | 1. Response rate (p < 0.05) 2. MMNCV (p < 0.05) 3. MSNCV (p < 0.05) 4. PMNCV (p < 0.05) 5. PSNCV (p < 0.05) | 8 w | Trial: 5 AEs/diarrhea (1), nausea (1), constipation (2), dizziness (1) Control: 1 AE/ nausea (1) |
Wang 2021a [105] | T1DM and T2DM/diagnostic criteria are presented without reference | Randomized; Single center; Parallel/Simple randomization using random number table | 30 (16/14) 64.63 ± 4.72 y | 30 (17/13) 64.71 ± 4.68 y | 1. Yiqiyangyintongluo decoction (200 mL, b.i.d.) 2. Epalrestat tablets (50 mg, t.i.d.) | 1. Epalrestat tablets (50 mg, t.i.d.) | 6.14 ± 1.24 y | 6.12 ± 1.22 y | 1. Response rate (p < 0.05) | 12 w | NR |
Wang 2021b [104] | T2DM/diagnostic criteria are presented without reference | Randomized; Single center; Parallel/Simple randomization using random number table | 50 (34/16) 67.13 ± 6.29 y | 50 (32/18) 67.13 ± 6.29 y | 1. Taohongsiwu decoction (b.i.d.) 2. Mecobalmin capsule (0.5 mg, t.i.d.) | 1. Mecobalamin capsule (0.5 mg, t.i.d.) | 1.57 ± 0.51 y | 1.42 ± 0.83 y | 1. MMNCV (p < 0.05) 2. MSNCV (p < 0.05) 3. PMNCV (p < 0.05) 4. PSNCV (p < 0.05) 5. TMNCV (p < 0.05) 6. TSNCV (p < 0.05) | 4 w | NR |
Zhang 2021 [106] | T2DM/Guidelines for the Prevention and Treatment of Diabetic Peripheral Neuropathy by Traditional Chinese Medicine, 2011 | Randomized; Single center; Parallel/NR | 74 Total 148 (78/70) 59.64 ± 8.94 y | 74 Total 148 (78/70) 59.64 ± 8.94 y | 1. Buqi Huoxue Zhitong decoction (b.i.d.) 2. α-Lipoic acid injection (0.6 g, q.d.) combined 0.9% Sodium chloride injection (250 mL, q.d.) | 1. α-Lipoic acid injection (0.6 g, q.d.) combined 0.9% Sodium chloride injection (250 mL, q.d.) | Total 9.33 ± 1.25 y | Total 9.33 ± 1.25 y | 1. TSNCV (p < 0.05) 2. PSNCV (p < 0.05) | 8 w | NR |
3.4. Pairwise Meta-Analysis
3.4.1. Response Rate
3.4.2. Motor Nerve Outcomes: MMNCV, PMNCV, UMNCV, TMNCV
3.4.3. Sensory Nerve Outcomes: MSNCV, PSNCV, USNCV, TSNCV
3.4.4. Safety Assessment
3.4.5. Sensitivity Analysis
3.4.6. Publication Bias
3.4.7. Quality of Evidence According to Outcome Measures
3.5. Network Meta-Analysis
3.5.1. Response Rate
3.5.2. Motor Nerve Outcomes: MMNCV, PMNCV, UMNCV, TMNCV
3.5.3. Sensory Nerve Outcomes: MSNCV, PSNCV, USNCV, TSNCV
3.5.4. Inconsistency Test
3.6. Analysis of the Mechanism of the ACP on DPN through Network Pharmacology
3.6.1. Active Ingredients and Anti-DPN Gene Targets of the ACP
3.6.2. Network Analysis of the ACP and DPN Targets
3.6.3. PPI Network Construction
3.6.4. Gene Ontology and KEGG Pathway Enrichment Analysis
4. Discussion
4.1. Summary of the Findings
4.2. Strengths and Limitations
4.3. Implications for Clinical Decision-Making
4.4. Implications for Drug Discovery
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Included Study | D1 | D2 | D3 | D4 | D5 | Overall |
---|---|---|---|---|---|---|
Jin 2004 [59] | Sc | H | H | L | Sc | H |
Sun 2008 [60] | Sc | H | H | Sc | Sc | H |
Shen 2009 [61] | L | H | H | L | Sc | H |
Lin 2010 [62] | Sc | H | H | L | Sc | H |
Wang 2010 [63] | L | H | H | L | Sc | H |
Yan 2010 [64] | Sc | H | H | Sc | Sc | H |
Wu 2011 [65] | Sc | H | H | L | Sc | H |
Gao 2012 [66] | Sc | H | H | L | Sc | H |
Gong 2013 [67] | Sc | H | H | L | Sc | H |
Han 2013 [68] | L | H | H | Sc | Sc | H |
Zhang 2013a [69] | L | H | H | L | Sc | H |
Zhang 2013b [70] | Sc | H | H | L | Sc | H |
Guo 2014 [71] | Sc | H | H | Sc | Sc | H |
Yang 2014a [73] | Sc | H | H | Sc | Sc | H |
Yang 2014b [72] | L | H | H | Sc | Sc | H |
Qi 2015 [74] | Sc | H | H | L | Sc | H |
Wang 2015 [75] | Sc | H | H | Sc | Sc | H |
Xue 2015 [76] | L | H | H | L | Sc | H |
Guo 2016 [77] | L | H | H | L | Sc | H |
Han 2016 [78] | Sc | H | H | L | Sc | H |
Lan 2016 [79] | H | H | H | L | Sc | H |
Mo 2016 [82] | L | H | H | Sc | Sc | H |
Wang 2016 [83] | L | H | H | Sc | Sc | H |
Li 2016a [80] | L | H | H | L | Sc | H |
Zhang 2016a [85] | L | H | H | L | Sc | H |
Li 2016b [81] | Sc | H | H | L | Sc | H |
Zhang 2016b [84] | L | H | H | L | Sc | H |
Chen 2017 [86] | L | H | H | L | Sc | H |
Shi 2017 [87] | Sc | H | H | L | Sc | H |
Wang 2017 [88] | L | H | H | L | Sc | H |
Chen 2018 [89] | L | H | H | Sc | Sc | H |
Dai 2018 [90] | H | H | H | L | Sc | H |
Hu 2018 [92] | Sc | H | H | L | Sc | H |
Huang 2018 [93] | L | H | H | L | Sc | H |
She 2018 [94] | L | H | H | L | Sc | H |
Xin 2018 [95] | H | H | H | Sc | Sc | H |
Gao 2019 [91] | Sc | H | H | L | Sc | H |
Wu 2019 [99] | L | H | H | L | Sc | H |
Yi 2019 [100] | L | H | H | L | Sc | H |
Ji 2019 [96] | L | H | H | Sc | Sc | H |
Liu 2019a [97] | Sc | H | H | L | Sc | H |
Liu 2019b [98] | Sc | H | H | Sc | Sc | H |
Chen 2021 [101] | Sc | H | Sc | L | Sc | H |
Hou 2021 [102] | Sc | H | H | L | Sc | H |
Li 2021 [103] | L | H | H | L | Sc | H |
Wang 2021a [105] | L | H | H | L | Sc | H |
Wang 2021b [104] | L | H | H | L | Sc | H |
Zhang 2021 [106] | H | H | H | L | Sc | H |
Intervention and Comparator Intervention | Outcomes | Number of Participants (Studies) | Anticipated Absolute Effects (95% CI) | Quality of the Evidence (GRADE) |
---|---|---|---|---|
EACP compared to CM for diabetic peripheral neuropathy | Response rate | 516 (7) | 224 more per 1000 (from 139 more to 318 more) | ⨁⨁⨁◯ MODERATE a |
ECCP compared to CM for diabetic peripheral neuropathy | Response rate | 1006 (11) | 134 more per 1000 (from 77 more to 196 more) | ⨁⨁◯◯ LOW a,c |
EAWP compared to CM for diabetic peripheral neuropathy | Response rate | 931 (11) | 184 more per 1000 (from 96 more to 283 more) | ⨁⨁◯◯ LOW a,c |
ECWP compared to CM for diabetic peripheral neuropathy | Response rate | 908 (12) | 190 more per 1000 (from 130 more to 255 more) | ⨁⨁◯◯ LOW a,c |
Characteristic | Response Rate | Motor Nerve Outcomes | Sensory Nerve Outcomes | ||||||
---|---|---|---|---|---|---|---|---|---|
MMNCV | PMNCV | TMNCV | UMNCV | MSNCV | PSNCV | TSNCV | USNCV | ||
Number of interventions | 16 | 7 | 10 | 5 | 7 | 9 | 10 | 9 | 7 |
Number of included trials | 42 | 14 | 21 | 9 | 4 | 20 | 21 | 13 | 6 |
Total number of patients in network | 3588 | 1365 | 2092 | 866 | 360 | 1894 | 2092 | 1348 | 523 |
Total possible pairwise comparisons | 120 | 21 | 45 | 10 | 5 | 36 | 45 | 36 | 21 |
Total number of pairwise comparisons with direct data | 18 | 7 | 10 | 4 | 4 | 10 | 10 | 8 | 6 |
Is the network connected? | TRUE | TRUE | TRUE | TRUE | FALSE | TRUE | TRUE | TRUE | TRUE |
Number of two-arm studies | 42 | 14 | 21 | 9 | 4 | 20 | 21 | 13 | 6 |
Number of multiple arm studies | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Average outcome (for continuous variables) | NA | 49.34 | 42.44 | 43.07 | 46.76 | 44.37 | 42.44 | 39.83 | 42.38 |
Total number of events in network (for dichotomous variables) | 2777 | NA | NA | NA | NA | NA | NA | NA | NA |
Number of studies with at least one zero events (for dichotomous variables) | 42 | NA | NA | NA | NA | NA | NA | NA | NA |
Number of studies with all zero events (for dichotomous variables) | 0 | NA | NA | NA | NA | NA | NA | NA | NA |
Mol ID | Mol Name | Structure | OB (%) | DL |
---|---|---|---|---|
MOL000359 | sitosterol | 36.91 | 0.75 | |
MOL000358 | beta-sitosterol | 36.91 | 0.75 | |
MOL011169 | Peroxyergosterol | 44.39 | 0.82 | |
MOL000073 | ent-Epicatechin | 48.96 | 0.24 | |
MOL000492 | (+)-catechin | 54.83 | 0.24 | |
MOL004576 | taxifolin | 57.84 | 0.27 | |
MOL001736 | (−)-taxifolin | 60.51 | 0.27 | |
MOL000387 | Bifendate | 31.10 | 0.67 | |
MOL000033 | (3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R,5S)-5-propan-2-yloctan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol | 36.23 | 0.78 | |
MOL000379 | 9,10-dimethoxypterocarpan-3-O-β-D-glucoside | 36.74 | 0.92 | |
MOL000296 | hederagenin | 36.91 | 0.75 | |
MOL000442 | 1,7-Dihydroxy-3,9-dimethoxy pterocarpene | 39.05 | 0.48 | |
MOL000374 | 5′-hydroxyiso-muronulatol-2′,5′-di-O-glucoside | 41.72 | 0.69 | |
MOL000422 | kaempferol | 41.88 | 0.24 | |
MOL000098 | quercetin | 46.43 | 0.28 | |
MOL000417 | Calycosin | 47.75 | 0.24 | |
MOL000439 | isomucronulatol-7,2′-di-O-glucosiole | 49.28 | 0.62 | |
MOL000354 | isorhamnetin | 49.60 | 0.31 | |
MOL000239 | Jaranol | 50.83 | 0.29 | |
MOL000371 | 3,9-di-O-methylnissolin | 53.74 | 0.48 | |
MOL000211 | Mairin | 55.38 | 0.78 | |
MOL000380 | (6aR,11aR)-9,10-dimethoxy-6a,11a-dihydro-6H-benzofurano [3,2-c]chromen-3-ol | 64.26 | 0.42 | |
MOL000438 | (3R)-3-(2-hydroxy-3,4-dimethoxyphenyl)chroman-7-ol | 67.67 | 0.26 | |
MOL000433 | FA | 68.96 | 0.71 | |
MOL000392 | formononetin | 69.67 | 0.21 | |
MOL000378 | 7-O-methylisomucronulatol | 74.69 | 0.30 | |
MOL000398 | isoflavanone | 109.99 | 0.30 |
Molecule Name | Degree Centrality | Betweenness Centrality | Closeness Centrality | Included Herb |
---|---|---|---|---|
quercetin | 45 | 0.636 | 0.632 | AR |
kaempferol | 23 | 0.140 | 0.460 | AR |
isorhamnetin | 13 | 0.067 | 0.413 | AR |
formononetin | 13 | 0.066 | 0.413 | AR |
7-O-methylisomucronulatol | 11 | 0.042 | 0.404 | AR |
Calycosin | 9 | 0.022 | 0.396 | AR |
3,9-di-O-methylnissolin | 8 | 0.034 | 0.387 | AR |
beta-sitosterol | 6 | 0.044 | 0.379 | CR |
Jaranol | 5 | 0.003 | 0.376 | AR |
(+)-catechin | 3 | 0.028 | 0.368 | CR |
Number | Gene Name | Degree Centrality | Betweenness Centrality | Closeness Centrality |
---|---|---|---|---|
1 | TNF | 45 | 0.054 | 0.846 |
2 | IL6 | 44 | 0.047 | 0.833 |
3 | VEGFA | 43 | 0.041 | 0.821 |
4 | TP53 | 41 | 0.042 | 0.797 |
5 | IL1B | 40 | 0.028 | 0.786 |
6 | PTGS2 | 38 | 0.025 | 0.764 |
7 | CAT | 37 | 0.046 | 0.753 |
8 | EGFR | 37 | 0.024 | 0.753 |
9 | JUN | 37 | 0.032 | 0.743 |
10 | NOS3 | 36 | 0.047 | 0.733 |
11 | PPARG | 36 | 0.037 | 0.733 |
12 | EGF | 35 | 0.014 | 0.733 |
13 | CCL2 | 34 | 0.013 | 0.724 |
14 | ESR1 | 33 | 0.033 | 0.714 |
15 | HMOX1 | 32 | 0.010 | 0.705 |
16 | MMP2 | 32 | 0.014 | 0.705 |
17 | VCAM1 | 30 | 0.009 | 0.688 |
18 | IFNG | 28 | 0.019 | 0.671 |
19 | IL2 | 28 | 0.004 | 0.671 |
20 | MPO | 26 | 0.008 | 0.655 |
21 | MAPK8 | 25 | 0.008 | 0.647 |
22 | SELE | 25 | 0.003 | 0.640 |
23 | MAPK14 | 24 | 0.002 | 0.632 |
24 | MMP3 | 24 | 0.022 | 0.632 |
25 | MAPK1 | 23 | 0.008 | 0.632 |
26 | KDR | 22 | 0.018 | 0.611 |
27 | MMP1 | 22 | 0.002 | 0.625 |
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Jo, H.-G.; Baek, E.; Lee, D. Comparative Efficacy of East Asian Herbal Formulae Containing Astragali Radix–Cinnamomi Ramulus Herb-Pair against Diabetic Peripheral Neuropathy and Mechanism Prediction: A Bayesian Network Meta-Analysis Integrated with Network Pharmacology. Pharmaceutics 2023, 15, 1361. https://doi.org/10.3390/pharmaceutics15051361
Jo H-G, Baek E, Lee D. Comparative Efficacy of East Asian Herbal Formulae Containing Astragali Radix–Cinnamomi Ramulus Herb-Pair against Diabetic Peripheral Neuropathy and Mechanism Prediction: A Bayesian Network Meta-Analysis Integrated with Network Pharmacology. Pharmaceutics. 2023; 15(5):1361. https://doi.org/10.3390/pharmaceutics15051361
Chicago/Turabian StyleJo, Hee-Geun, Eunhye Baek, and Donghun Lee. 2023. "Comparative Efficacy of East Asian Herbal Formulae Containing Astragali Radix–Cinnamomi Ramulus Herb-Pair against Diabetic Peripheral Neuropathy and Mechanism Prediction: A Bayesian Network Meta-Analysis Integrated with Network Pharmacology" Pharmaceutics 15, no. 5: 1361. https://doi.org/10.3390/pharmaceutics15051361