Table 3.
Summary of articles on complementary and alternative medicine therapies for muscular atrophy (in vivo + in vitro).
| Authors | Design | Origin | Group / Sample Size (n) | Sample Model | Duration | Outcome Measures | Quantity and Type of Intervention | Main Outcomes |
|---|---|---|---|---|---|---|---|---|
| Kim AY 2016 [32] |
In vivo/ In vitro |
Korea | In vivo Total n = 20 No tumor (5) Tumor + Saline (5) Tumor + SO50 (5) Tumor + SO100 (5) |
In vivo: CT-26 s.c injection tumor-bearing mice (BALB/c mice, 6 wk, M) |
In vivo: 18 d |
In vivo: (1) Body weight (2) Muscle weight (3) NO, inflammatory cytokines (4) phos-p38, IкBα, IKKαβ, STAT3 |
Sosiho-tang (SO) In vivo: (i) SO: fed 50 or 100 mg/kg, days 10 to 27 after tumor inoculation (ii) Control: fed saline |
In vivo: (1) Body weight: Normal > T + SO (100) > T + SO (50) > T + Saline (2) Muscle weight: Normal ≒ T + SO (100) ≒ T+SO (50) > T + Saline (3) NO: dose-dependently suppress (p<0.05 vs. control) IL-6, IL-1α, TNF-α, IL-1β: T + Saline > T + SO (p<0.05) (4) phos-p38↓, IкBα↓, IKKαβ↓, STAT3↓: T + Saline > T+SO |
| In vitro CON SO-0, -50, -100 |
In vitro: CT-26-mediated C2C12 myoblast |
In vitro: 48 h | In vitro: (1) IL-6, TNF-α (2) Muscle wasting & myotubes |
In vitro: (i) SO powder dissolved in 10% DS to 50 μg/ml, 100 μg/ml for 48 h |
In vitro: (1) IL-6, TNF-α: T + Saline > T+SO (10) > T+SO (50) >T+SO (100) (p<0.05 vs. control) (2) Muscle wasting↓ Intact myotubes↑ |
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| Zhang ZK 2016 [33] |
In vivo/ In vitro |
China | In vivo: Baseline (10) Age-matched control (10) HS (10) L-ICT + HS (10) H-ICT + HS (10) W (10) L-ICT + W (10) H-ICT + W (10) |
In vivo: Rats with or without wortmannin inj. (15 μm/kg/day) for 28 d HS (SD rat, 3 mo, M) |
In vivo: 28 d | In vivo: (1) Mass outcome (muscle weight, fiber CSA) (2) Muscle function |
ICT: Icaritin In vivo: (i) Low ICT (L-ICT): 80 mg/kg/day (ii) High-ICT (H-ICT): 120 mg/kg/day, oral intake |
In vivo: (1) Mass outcome: HS < L-ICT + HS < H-ICT + HS < Baseline (p<0.05) W < L-ICT + W < H-ICT + W < Baseline (p<0.05) (2) Functional outcome: HS < L-ICT + HS < H-ICT + HS < Baseline (p<0.05) W < L-ICT + W < H-ICT + W < Baseline (p<0.05) |
| In vitro: CON ICT 5, 10, 20 |
In vitro: Wortmannin (W) pre-incubated C2C12 cell |
In vitro: 24 h |
In vitro (1) PI3K/Akt signaling proteins |
In vitro: ICT 5 μM or 10 μM or 20 μM for 24 h |
In vitro: (1) PI3K-p110, p-Akt, p-mTOR, p70S6K, p-4EBP1: ICT > ICT+W > W (p<0.05) FOXO1, FOXO3a: ICT < ICT+W < W (p<0.05) Atrogin-1, MuRF-1: ICT < ICT + wort < wort (p<0.05) Atrogin-1, MuRF-1: Control > ICT10 > ICT20 (p<0.05 vs. CON) |
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| Sung BK 2015 [34] |
In vivo/ In vitro |
Korea | In vivo: Young-Control (YC) Young-LE (YL) Old-Control (OC) Old-LE (OL) (n = 4~6 per group) |
In vivo: Young SD rat (5 mo, M) Old SD rat (18-19 mo, M) |
In vivo: 35 d |
In vivo: (1) Muscle mass (2) Muscle function (3) Muscle CK activity |
In vivo: Loquat leaf extract (LE) fed 50 mg/kg/day for 35 d |
In vivo: (1) Muscle mass: OL > OC (p<0.05) (2) Muscle strength: OL > OC (p<0.05) (3) CK activity: OL > OC (p<0.05) |
| In vitro: CON LE 0.25, 0.5, 1.0, 2.5 |
In vitro: C2C12 myoblasts (untreated) |
In vitro: 24 h |
In vitro: (1) C2C12 viability (2) Myogenic proteins (3) CK activity (4) Akt/mTOR pathway |
In vitro: LE 0.25, 0.5, 1.0, 2.5 μg/ml for 24 h |
In vitro: (1) Cell viability: control < LE (2) MyHC, MyoD: control < LE 0.25 < LE 0.5 < LE 1.0 < LE 2.5 (3) CK activity: control < LE 1.0 < LE 2.5 (p<0.01) (4) PI3K, Akt, mTOR: control < LE |
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| Lu L 2016 [35] |
In vivo/ In vitro |
China | In vivo Total n = 160 Sham OP (SOP) (40) OP (40) OP + APS (40) SOP + APS (40) |
In vivo: 5/6 nephrectomized SD rats (SD rat, 6 wk, M) |
In vivo: 155 d |
In vivo: (1) Body weight (2) Cross-sectional area (3) p-Akt/mTOR, MuRF1/MAFbx and Autophagy signaling (4) Amino acid carriers (5) Pro-inflammatory & Oxidative factor |
In vivo: Control: Normal diet, Sham OP APS: Normal diet with 2% Astragalus polysaccharide |
In vivo: (1) Body weight: OP < OP+APS < SOP (p<0.05) (2) Mean CSA: OP + APS > OP (p<0.05) (3) p-Akt, mTOR: OP < OP + APS (p<0.05) MuRF1, MUFbx: OP > OP + APS (p<0.05) Atg7, LC3B: OP > OP + APS (p<0.05) (4) SLC38A2, ATF4: OP < OP + APS (p<0.05) (5) TNF-α, IL-15, CRP: OP > OP + APS (p<0.05) MDA: OP > OP + APS (p<0.05) SOD: OP < OP + APS (p<0.05) |
| In vitro Control TNF-α TNF-α + APS 0.05, 0.1, 0.2, 0.5, 1, 2 |
In vitro: TNF-α treated C2C12 cell |
In vitro: 48 h |
In vitro: (1) Myotube diameter (2) Akt/mTOR, ubiquitin proteasome, autophagy signaling |
In vitro: APS: 0.05, 0.1, 0.2, 0.5, 1, 2 mg/mL APS 80 ng/mL TNF-α treated |
In vitro: (1) Myotube diameter: Control < APS (p<0.05) (2) p-mTOR: Control < APS (p<0.05) LC3B-II/LC3B-I ratio: Control > APS (p<0.05) |
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| Cho SG 2018 [36] | In vivo/ In vitro | Korea | In vivo Total n = 48 normal (8) CON (8) SC 20 (8) SC 100 (8) SSLE 20 (8) SSLE 100 (8) |
In vivo: Hindlimb suspension rat model (SD rats, 6 wk, M) |
In vivo: 21 d |
In vivo: (1) Muscle weight (2) Muscle strength (3) CSA |
∗SC: Schisandra chinensis (Turcz.) Baill ∗LC: Lycium chinense Mill ∗EU: Eucommia ulmoides Oliv SSLE: 2:1:1-SC:LC:EU herb pair SLE: 1:1:1-SC:LC:EU In vivo: (orally) (i) 20: 20mg/kg (ii) 100: 100mg/kg |
In vivo: (1) Muscle weight (a) Gastrocnemius: CON < SC20 < SC100 < SSLE20 < SSLE100 (p<0.001 ver CON) (b) Soleus: CON < SC20 < SC100 (p<0.05) / CON < SSLE20 < SSLE100 (p<0.001) (c) Tibialis ant: CON < SSLE100 (p<0.01) (2) Muscle strength: CON < SC100, SSLE20 (p<0.01), SSLE100 (p<0.001) (3) CSA: CON < SC100, SSLE20, SSLE100 (p<0.001) |
| In vitro TNF LC EU SC SLE SSLE |
In vitro: TNF-α treated C2C12 cell |
In vitro: 24 h |
In vitro: (1) Myotube diameter (2) Protein synthesis (ubiquitin-proteasome system) |
In vitro: 200 μg/ml | In vitro: (1) Myotube diameter: CON < LC, EU, SC, SLE, SSLE (p<0.001) (2) atrogin-1↓ with SC, SLE, SSLE (p<0.001 vs CON) (3) MuRF-1↓ with LC, EU, SLE, SSLE (p<0.001 vs CON) (4) MyoD↑ with LC, EU, SC, SLE, SSLE (p<0.001 vs CON) (5) Myogenin↑ with EU, SC, SLE, SSLE (p<0.001 vs CON) (6) p-Akt ↑, p-mTOR↑ with LC, EU, SC, SLE, SSLE (p<0.01 vs CON) |
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| Zhu M 2017 [37] | In vivo/ In vitro | China | In vivo Total n = 24 CON (8) HS (8) BZ (8) |
In vivo: Hindlimb suspension rat model (Kunming mice, 8 wk, M) |
In vivo: 21 d |
In vivo: (1) Muscle weight (2) CSA (3) Muscls strength |
In vivo: BZ: Bu Zhong Yi Qi decoction 5.93mg/g/day orally |
In vivo: (1) Muscle weight (a) Gastrocnemius: HS < BZ (p<0.05) (b) Soleus: HS < BZ (p<0.05) (2) CSA: HS < BZ (p<0.05) (3) Muscle strength: HS < BZ (p<0.01) |
| In vitro RS BZ |
In vitro: C2C12 myoblasts (untreated) |
In vitro: n r |
In vitro: (1) NCoR1 (nuclear receptor corepressor 1) (2) Myogenesis |
In vitro: RS: rat serum BZ: Bu Zhong Yi Qi decoction |
In vitro: (1) NCoR1↓ (p<0.001 vs RS) (2) Pax7↑ (p<0.05), Myogenin↑, MyHC↑ (p<0.01) |
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| Geng Z 2017 [38] | In vivo/ In vitro | China | In vivo Total n = 32 NOR (8) CON (8) APS (8) KT (8) |
In vivo: 5/6 nephrectomized rat model (SD rat, 7-8 wk, M) |
In vivo: 6 wk |
In vivo: (1) Atrogin and ubiquitin |
APS: Astragalus polysaccharide, 3g/kg/day for 6 weeks, intraperitoneally / in vitro: 15 mg/1 KT: ketosteril (α-ketoacid tablets), 1ml/200g/day for 4 weeks, intravenously CON: saline, 3g/kg/day for 6weeks, intraperitoneally NOR: Sham-OP PDTC: pyrrolidine dithiocarbamate 50 μmol/1 |
In vivo: (1) Atrogin-1: APS < KT < CON (p<0.05 vs CON) Ubiquitin: APS < KT < CON (p<0.05 vs CON) |
| In vitro TNF TNF+APS TNF+PDTC |
In vitro: TNF-α treated rat L6 myoblasts |
In vitro: 48 h |
In vitro: (1) Atrogin and ubiquitin (2) Muscle cell diameter |
In vitro: (1) Atrogin-1↓, Ubiquitin↓ in APS (p<0.05 vs CON) (2) Cell diameter↑ in APS (p<0.05 vs CON) (3) Atrogin-1↓, Ubiquitin↓ in PDTC (p<0.05 vs CON) (4) Cell diameter↑ in PDTC (p<0.05 vs CON) |
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| Kim AY 2018 [39] | In vivo/ In vitro | Korea | In vivo Total n = 15 CON (5) SGE10 (5) SGE50 (5) |
In vivo: CT-26 colon carcinoma-implanted mice (BALB/c mice, 6 wk, M) |
In vivo: 15 d |
In vivo: (1) Body weight (2) Muscle weight (3) IL-6 |
SGE: herbal cocktail composed of Ginseng Radix alba, Atractylodis Rhizoma alba, and Hoelen In vivo: SGE 10mg/kg/day or 50mg/kg/day for 15days, orally |
In vivo: (1) Body weight: CON < SGE10 (p<0.01), SGE50 (p<0.05) (2) Muscle weight: CON < SGE50 (p<0.01) (3) Serum IL-6: CON > SGE10 > SGE50 (p<0.01) |
| In vitro SGE 5 SGE 10 SGE 25 SGE 50 |
In vitro: CT-26-mediated C2C12 myoblast |
In vitro: 48 h | In vitro: (1) Inflammatory cytokines (2) NO production and MAPK/NF-κB activation (3) Muscle cell proliferation protein |
In vitro: SGE 5, 10, 25, 50μg/mL, incubated for 48h |
In vitro: (1) IL-1β↓ (5,10,25,50 p<0.01), IL-6↓ (10,25,50 p<0.01), TNF-α↓ (25 p<0.05, 50 p<0.01) (2) NO↓ (10,25,50 p<0.01), iNOS↓ (25,50 p<0.01), p-p38↓, p-ERK↓, p-JNK↓, p-IκBα↓ (25,50 p<0.01) (3) MyH↑ (10,25,50 p<0.01) |
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| Tseng YT 2017 [40] |
In vivo/ In vitro | China | In vivo Total n = 32 WT (wild-type) (8) CON (8) LWDH15 (8) LWDH30 (8) |
In vivo: Survival motor neuron (SMN) deficiency-induced transgenic mice model (n r, n r, M) |
In vivo: not limited In vitro: 48 h |
In vivo: (1) SMN expression in muscle (2) Muscle strength (3) Body weight |
LWDH: Liuwei dihuang water extract In vivo: 15mg/kg/day, 30mg/kg/day, orally |
In vivo (1) Survival motor neuron expression: CON < LWDH30 (p<0.001) (2) Hindlimb score: CON < LWDH30 (p<0.001) (3) Body weight: WT > LWDH30 (p<0.01) > LWDH15 (p<0.05) > CON |
| In vitro CON LWDH 0.01, 0.1, 1, 10 |
In vitro: NSC34 motor neuron-like cell (transfected to SMN deficiency) |
In vitro: (1) Apoptotic-related pathway |
In vitro: 0.01, 0.1, 1, 10μg/mL | In vitro (1) Bcl-2↑, cytochrome c↓, cleaved-caspase-3↓ |
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