A Review of Complementary and Alternative Medicine Therapies on Muscular Atrophy: A Literature Review of In Vivo/In Vitro Studies

Table 2

Summary of articles on complementary and alternative medicine therapies for muscular atrophy (in vivo).

First Author (year) (Ref)	Design	Origin	Group / Sample-Size (n)	Sample Model (Age) (M/F)	Duration	Outcome Measures	Quantity and Type of Intervention	Main outcomes
Onda A 2011 [5]	In vivo	Japan	Total n = 28; control (7); HS (7); HS + MA (7); HS + EA (7)	Hindlimb suspension (HS) rat model; (C57BL/6, 8 wk, M)	2 wk	(1) Muscle weight/body weight; (2) Cross sectional area (CSA); (3) Muscle-proteolytic genes; (4) Protein synthesis markers	MA (manual acupuncture): 30 min on the gastrocnemius, 5 mm insert; EA (electro-acupuncture): 30 min on the gastrocnemius, 5 mm insert, 1 Hz, 6.5 mA; 1/day for 2wk	(1) Muscle/body weight: HS < HS+MA (7%, p<0.05); HS < HS+EA (10%, p<0.001); (2) CSA: HS > HS+EA (p<0.05); (3) Atrogin-1↓, MuRF1↓ in EA (p<0.01 vs. HS); Atrogin-1↓ in MA (p<0.01 vs. HS); (4) Akt1↑, TRPV4↑ in MA (p<0.05 vs. HS)
Su Z; 2015; [6]	In vivo	China	Total n = 48; control (12); LFES (12); Diabetes (12); Diabetes + LFES (12)	Streptozotocin-induced diabetic mouse model; (C57BL/6, 8-10 wk, M)	2 wk	(1) Muscle grip function; (2) Muscle weight/body weight; (3) Muscle regeneration proteins; (4) Protein synthesis markers	LFES (Low-frequency electric; stimulation): positive point at GB34,; negative point at ST36; 20 Hz, 1 mA for 15 min; 1/day for 2wk	(1) Muscle grip function: DM + LFES > DM (p<0.05); (2) Muscle weight (Soleus, Extensor digitorum longus): DM + LFES > DM (p<0.05); (3) Pax7↑, MyoD↑, myogenin↑, eMyHC↑ (p<0.05 vs. DM); (4) IGF-1↑, p-Akt↑, mTOR↑, p70S6K↑ (p<0.05 vs. DM)
Dong Y 2015; [7]	In vivo	China	Total n =72; Control + Saline (12); Control + BJ (12); Control + AP (12); COPD + Saline (12); COPD + BJ (12); COPD + AP (12)	Klebsiella pneumoniae & cigarette smoke-induced COPD rat model; (Sprague-Dawley (SD) rat, 2 mo, M/F)	12 wk	(1) Muscular tension; (2) Muscular fatigue index; (3) Expressions of Bnip3 and Cyto-C in muscle tissues	BJ: Bufei Jianpi granules; (5 g·kg^−1·d^−1); AP: Aminophylline; (2.3 mg·kg^−1·d^−1); Intragastrically inserted	(1) Muscular tension: BJ > Saline, AP (p<0.05); (2) Muscular fatigue: BJ < Saline, AP (P<0.05); (3) Bnip3↓, CytoC↓ (p<0.05 vs. Saline, AP)
Zhuang P 2016 [8]	In vivo	China	Total n = 60; Normal + Water (C) (20); Tumor + Water (M) (20); Tumor + ZBHP (20)	C26-colon- adenocarcinoma-implanted mice; (C57BL/6, 4-6 wk, M)	19 d	(1) Muscle weight; (2) Muscle function; (3) Pro-inflammatory cytokines; (4) Atrophy-related genes; (5) IGF-1/Akt and autophagy pathway	ZHBP: Zhimu (Rhizoma Anemarrhena) and Huangbai (Cortex Phellodendri) 1:1 extracted with ethanol; 104 mg/kg/day, oral intake	(1) Muscle weight: ZHBP > M (p<0.05); (2) Grip-strength: ZHBP > M (p<0.01); (3) TNF-α, IL-6: ZHBP < M (p<0.05); IGF-1: ZHBP > M (p<0.01); (4) Atrogin-1↓, MuRF1↓ (p<0.05 vs. M); (5) SRIT1↑, p-Akt↑, FOXO3↓ (p<0.05 vs. M)
Kishida Y 2014 [9]	In vivo	Japan	Total n = 41; SAMP8 + N (10); SAMP8 + GJG (10); SAMR1 + N (10); SAMR1 + GJG (11)	Senescence-accelerated rat model (SAMP8); Senescence-accelerated aging-resistant rat model (SAMR1); (7 wk, M)	38 wk	(1) Muscle fiber size; (2) Myofiber balance (fast/slow); (3) Glycogen synthesis proteins; (4) Muscle atrophy proteins	GJG: Go-sha-jinki-Gan; 4% (w/w) GJG daily for 38 wk; N (Control): normal diet	(1) Muscle fiber: P8+N < P8+GJG (p<0.0001); (2) Fast skeletal muscle: P8+N <P8+ GJG (p<0.0001); p-AMPK↑, PGC-1α↑ in P8+GJG; (3) IGF-1↑, p-Akt↑, p-GSK3β↑; (4) p-FoxO4↑, MuRF1↓, TNF-α↓
Hu L; 2015 [10]	In vivo	China	Total n = 48; Sham (Sham op) (12); Sham-LFES (12); CKD (12); CKD-LFES (12)	5/6-nephrectomized rat model (mice with chronic kidney disease) (n r, n r, n r)	15 d	(1) Muscle mass (soleus & extensor digitorum longus); (2) Grip strength meter; (3) Synthesis-related proteins; (4) IGF-1 and MGF	LFES: Low-frequency electric; Stimulation acupuncture; positive point (GB34); negative point (ST36), 20Hz, 1mA 15 min 1/day for 15 d needles: 0.25 mm (diameter)	(1) Muscle mass: Sham ≒ Sham-LFES; CKD < CKD-LFES (p<0.05); (2) Muscle function: CKD < CKD-LFES (p<0.05); (3) p-Akt, mTOR, p70S6K: CKD < CKD-LFES (p<0.05); (4) IGF-1, MGF: CKD < CKD-LFES (p<0.05)
Nakashima Y; 2014 [11]	In vivo	Japan	Total n = 16; Control (8); CSD (8)	ALDH22 Tg rat model; (selectively decrease ALDH2 activity); (C57BL/6 mice, n r, M)	6 mo	(1) Oxidative stress marker; (2) Muscle tissue injury marker; (3) Body weight; (4) Gastrocnemius cell size; (5) Mitochondrial cytochrome C oxidase activity	CSD: Chlorella-supplemented diet 1% for 6 mo; Control: fed basic diet	(1) Urinary isoprostane: CSD < Control (after 4 mo, p<0.05); MDA, HAE: CSD < Control (p<0.01); (2) CPK activity: CSD < Control (p<0.05); CKMB activity: CSD < Control; (3) Body weight: CSD > Control (after 4 mo, p<0.05); (4) Cell size: CSD > Control (p<0.05); (5) Cyto-C oxidase activity: CSD < Control (p<0.01)
Kim MJ; 2012; [12]	In vivo	Korea	Total n = 12; Control (4); CIA (4); CIA+Moxi (4)	Collagen-induced arthritis (CIA) rat model (Inj of bovine type II collagen); (DBA/1J mice, 6 wk, M)	3 wk	(1) Cross-sectional area; (2) Phospho-ERK1/2; (3) Myostatin protein; (4) IGF-1 mRNA	Moxi: Moxibustion BL23 (shenshu), ST36 (zusnali) on both sides; 5 times/day every other day for 3 wk; Kangwha-moxi cone 0.025g per 1point	(1) CSA: Control > CIA+Moxi > CIA (p<0.05); (2) phospho-ERK1/2: CIA > CIA+Moxi; (3) Myostatin protein: CIA > CIA+Moxi; (4) IGF-1: CIA+Moxi > CIA
Kim JW; 2015 [13]	In vivo	Korea	Total n = 48; Control (8); Dexa control (8); Dexa + OM (8); Dexa + FS125 (8); Dexa + FS250 (8); Dexa + FS500 (8)	Dexamethasone-induced muscle atrophy mice; (SPF/VAF mice, n r, n r)	24 d	(1) Muscle mass; (2) Muscle strength; (3) Serum biochemistry; (4) Antioxidant defense factor; (5) mRNA expression	FS: Fructus Schisandrae extract 125, 250, 500mg/kg, 1/day for 24 d oral intake; OM: Oxymetholone 50 mg/kg	(1) Muscle mass; (a) Body weight: Dexa < FS125 < FS250 < OM < FS500 (p<0.01); (b) Calf, Gastrocnemius thickness: Dexa < FS 125 < FS250 < FS 500 < OM (p<0.01); (2) Muscle strength: Dexa < FS250, FS500 (p<0.01); (3) Serum creatine↓, CK↓, LDH↑ (p<0.01 vs. Control); (4) MDA↓, ROS↓, GSH↓, SOD↓, CAT↓; (5) Atrogin-1↓, MuRF1↓, SIRT1↓, PI3K↑, Akt1↑, A1R↑ (p<0.05 vs. control)
Zhang J; 2014 [14]	In vivo	China	Total n = 45; Normal (C) (15); Diabetes (M) (15); Diabetes + ZB (15)	Insulin deficiency rat model by low-dose STZ injection; (C57BL/6, 12 wk, M)	6 wk	(1) Muscle weight; (2) Muscle function; (3) Myofiber CSA; (4) IGF1, Akt/mTOR/FoxO3 signal pathways	ZB: Zhimu-Huangbai (1:1) herb pair 0.1ml/10g, 1/day for 6 wk; C, M: Normal saline treated	(1) Muscle (quadriceps) weight: ZB > M (p<0.05); (2) Muscle strength: ZB > M (p<0.01); (3) CSA: ZB > M (p<0.05); (4) IGF-1↑, Akt↑, mTOR↑, p-S6K1↑, FoxO3↓ (p<0.05 vs M)
Jang SO; 2009 [15]	In vivo	Korea	Total n = 48; Control (24); Sample (PR) (24)	Sciatic nerve-damaged rat model; (SD rat, 10 wk, M)	12 d	(1) Muscle weight; (2) Cross-sectional area; (3) Bax, Bcl-2	PR: Puerariae Radix extract, 25.0mg/100g, 1/day for 12 d oral intake	(1) Muscle weight: Control < Sample (p<0.05); (2) CSA: Control < Sample (p<0.05); (3) Bcl-2↑, Bax↓ (p<0.05)
Kim BH 2016 [16]	In vivo	Korea	Total n = 30; Normal (10); EtOH (10); EtOH + DKEJ (10)	EtOH-treated rat model; (SD rat, 10 wk, M)	8 wk	(1) Body weight; (2) Muscle weight; (3) Cross-sectional area	DKEJ: Daekumeumja; 28.0mg/100g, 1/day for 8 wk	(1) Body weight: EtOH < EtOH + DKEJ (p<0.05); (2) Muscle weight: EtOH < EtOH + DKEJ (p<0.05); (3) CSA: EtOH < EtOH + DKEJ (p<0.05)
Cho JH; 2008 [17]	In vivo	Korea	Total n = 36; Sham-OP (12); Control (OP) (12); OP + EC (12)	Sciatic nerve-damaged rat model; (SD rat, 10 wk, M)	12 d	(1) Muscle weight; (2) Cross-sectional area; (3) Bax, Bcl-2	EC: Eucommiae Cortex extract 170mg/100g, 1/day for 12d	(1) Muscle weight: Sham-OP > EC > Control (p<0.05); (2) CSA: Sham-OP > EC > Control (p<0.05); (3) Bax↓, Bcl-2↑
Lee CW 2007 [18]	In vivo	Korea	Total n = 24; Sham (8); Control (MCAO) (8); Sample (MCAO + DR) (8)	Middle cerebral artery occlusion (MCAO) stroke rat model; (SD rat, 10 wk, M)	25 d	(1) Muscle fiber type; (2) Cross-sectional area; (3) MHC-II; (4) MyoD expression	DR: Dipsaci Radix; 184.4 mg/100g, 1/day for 25d, oral intake	(1) Muscle fiber type (type-I): Control < Sample (p<0.01); (2) CSA: not significant; (3) MHC-II↓; (4) MyoD: Control < Sample (p<0.01)
Han SW; 2008; [19]	In vivo	Korea	Total n = 18; Sham (6); Control (6); Sample (6)	MCA occlusion stroke rat model; (SD rat, 10 wk, M)	4 wk	(1) Muscle fiber type; (2) Cross-sectional area; (3) MyoD expression	DR: Dipsaci Radix; 184.4mg/100g, 1/day for 4 wk, oral intake	(1) Muscle fiber type: type-I ↑, type-II ↓ (p<0.05 vs. control); (2) CSA: control < Sample (p<0.05); (3) MyoD↑ (p<0.05 vs. control)
Kim BH 2017 [20]	In vivo	Korea	Total n = 30; Normal (10); EtOH (10); EtOH + PR (10)	Alcohol-induced (EtOH) muscle atrophy rat model; (SD rat, 10 wk, M)	4 wk	(1) Muscle weight; (2) Cross-sectional area; (3) Bcl-2, Bax	PR: Pueraria radix 4.6mg/100g, 1/day for 4 wk, oral intake	(1) Muscle weight: EtOH + PR > EtOH (p<0.05); (2) CSA: EtOH + PR > EtOH (p<0.05); (3) Bcl-2↑, Bax↓ (p<0.05 vs. EtOH)
Soh KS 2009 [21]	In vivo	Korea	Total n = 24; Normal (6); Control (6); HS (6); HS + KS (6)	Hindlimb suspension rat model; (SD rat, 6 wk, M)	2 wk	(1) Muscle weight; (2) IGF-1 protein; (3) Myogenin protein; (4) MyoD protein	KS: KangwhalSokdan-tang; 1 mg/100g, 3 times/1day orally	(1) Muscle weight: HS < HS+KS (p<0.001); (2) IGF-1: HS < HS+KS (p<0.05, in Type I); (3) Myogenin: not significant; (4) MyoD: HS < HS+KS (p<0.05 in Type I)
Kim BH 2016 [22]	In vivo	Korea	Total n = 30; Normal (10); EtOH (10); EtOH + SHSGS (10)	Alcohol-induced (EtOH) muscle atrophy rat model; (SD rat, 10 wk, M)	4 wk	(1) Muscle weight; (2) CSA; (3) Apoptotic factor	SHSGS: Shihosogan-san; 31.5 mg/100g, 1/day for 4 wk, orally	(1) Muscle weight: not significant; (2) CSA: not significant; (3) Bcl-2↑, Bax↓ (p<0.05 vs. EtOH)
Kim BH 2017 [23]	In vivo	Korea	Total n = 20; Control (CON) (10); DYJ (10)	Hindlimb suspension rat model; (SD rat, 10 wk, M)	2 wk	(1) Muscle weight; (2) CSA; (3) Apoptotic factor	DYJ: Daeyeoung-jeon 259.6mg/100g/day orally; CON: Saline, orally	(1) Muscle weight: CON < DYJ (p<0.05); (2) CSA: CON < DYJ (p<0.05); (3) Bax↓, Bcl-2↑ (p<0.05 vs. CON)
Kim BH 2017 [24]	In vivo	Korea	Total n = 20; CON (10); DGBHT (10)	Hindlimb suspension rat model; (SD rat, 10 wk, M)	2 wk	(1) Muscle weight; (2) CSA; (3) Malondialdehyde (MDA); (4) Cu/Zn-SOD activation	DGBHT: Dangguibohyul-tang 236.7mg/100g/day orally; CON: Saline, orally	(1) Muscle weight: CON < DGBHT (p<0.05); (2) CSA: CON < DGBHT (p<0.01); (3) MDA: no significant difference; (4) Cu/Zn-SOD: CON < DGBHT (p<0.05)
Wang D 2017 [25]	In vivo	China	Total n = 30; CON (10); JPYS (10); Sham-OP (10)	5/6 nephrectomized rat model (SD rat, n r, M)	6 wk	(1) Renal function; (2) Muscle weight; (3) CSA; (4) Protein synthesis and protein degradation; (5) Ubiquitin-proteasome system and FoxO3a activation; (6) Mitochondrial biogenesis proteins; (7) Muscle autophagy/mitophagy pathway; (8) Mitochondrial dynamics	JPYS: Jian-Pi-Yi-Shen decoction, 10.89mg/kg/day orally	(1) BUN, Creatinine: CON > JPYS (p<0.001); (2) Muscle weight: CON < JPYS (p<0.05); (3) CSA: CON < JPYS (p<0.05); (4) Protein synthesis↑, degradation↓ (p<0.05 vs CON); (5) Atrogin-1↓, MuRF-1↓, p-FoxO3a↑, FoxO3a↓ (p<0.05 vs. CON); (6) Cox IV↑, NRF-1↑, PGC-1α↑ (p<0.05 vs. CON); (7) LC3II/LC3I ratio↓, Beclin-1↓, P62↓, PINK1↓, Parkin protein level↓ (p<0.05 vs. CON); (8) Fis1↓, Mfn2↑ (p<0.01 vs CON), Drp-1↓, OPA-1↑ (p<0.05 vs. CON)
Su Z 2017 [26]	In vivo	China	Total n = 36; Sham-OP (9); Sham+LFES (9); CKD (9); CKD+LFES (9)	5/6 nephrectomized rat model (C57/BL6 mice, 2-4 mo, M)	2 wk	(1) Autophagosome-proteolysis pathway	LFES: positive point-GB34, negative point-ST36; 20Hz, 1mA for 15min	(1) Bnip3↓, Beclin-1↓, LC3II/I ratio↓ (p<0.05 vs. CKD)
Zhou L 2018 [27]	In vivo	China	Total n = 56; Sham-OP (8); Model (DSMA) (8); CON-siRNA +BYHWT (8); ANGPTL4-siRNA +BYHWT (8); BYHWT low (8); BYHWT moderate (8); BYHWT high (8)	Denervated-dependent skeletal muscle atrophy (DSMA) rat model; (SD rat, 8-10 wk, M)	2 wk	(1) ANGPTL4 in pathogenesis of DSMA (on Anti-inflammatory effect); (2) Muscle cell apoptosis; (3) NF-кB and MURF1 expression	BYHWT: Buyang Huanwu Tang; (high: solution diluted 2X / moderate: 4X / low: 8X), 2ml every day, orally; Model: DSMA + saline; ANGPTL4: angiopoietin-like protein 4	(1) Inflammatory Cells: Model > ANGPLT4-siRNA+BYHWT > CON-siRNA+BYHWT (p<0.05); (2) Cell apoptosis: Model > BYHWT-low > BYHWT-moderate > BYHWT-high (p<0.01 vs. Model); (3) NF-кB p65, MURF1: Model > BYHWT-low > BYHWT-moderate > BYHWT-high (p<0.05 vs. Model)
Yu J 2017 [28]	In vivo	China	Total n = 54; NOR (6); SNI 1wk, 2wk, 4wk, 6wk (6 each); NOR+EA 4wk, 6wk (6 each); SNI+EA 4wk, 6wk (6 each)	Penicillin injection-induced sciatic nerve injury (SNI) rat model; (SD rat, 7-9 wk, M)	2 wk/ 4 wk	(1) Sciatic nerve functional indices (SFI); (2) Muscle weight; (3) Muscle fibre CSA; (4) mRNA expression of agrin, AChR-ε and AChR-γ	EA: Electro-acupuncture at GB30 (positive) and ST36 (negative); 5Hz, 2mA for 30min; 1 course: alternate days, three times a week for 2 weeks; 2 course: alternate days, three times a week for 4 weeks; 1w, 2w, 4w, 6w: euthanased at 1,2,4,6weeks	(1) SFI: SNI < SNI+EA (p<0.05); (2) Muscle weight: SNI < SNI+EA (p<0.05); (3) CSA: SNI < SNI+EA (p<0.05); (4) agrin↑, AChR-ε↑, AChR-γ↓ (p<0.05 vs. SNI)
Zhang YH; 2017 [29]	In vivo	China	Total n = 72; SCI (18); TANES (18); EA (18); Sham-OP (18)	Spinal cord transection surgery treated rat model (SD rat, n r, F)	4 wk	(1) Motor neurons of L3, L5; (2) Neurotransmitter synthetase (ChAT); (3) Neurotrophin-3 (NT-3) expression; (4) Muscle weight; (5) CSA	TANES: Tail nerve electrical stimulation 2.5-8.0kHz(mid),; 1-150Hz(low), 100mA, 20min 5times/week for 4weeks; EA: electroacupuncture, GV6, GV9, GV2, GV1, ST36, 60Hz for 1.05s and 2Hz for 2.85s, pulse width 0.5ms, 2min, every other day for 4weeks; SCI: spinal nerve injury	(1) Motor neuron L3: SCI < TANES, EA (p<0.05); L5: SCI < TANES, EA (p<0.05); (2) ChAT (choline acetyltransferase): SCI < TANES, EA (p<0.05); (3) NT-3: SCI < TANES, EA (p<0.05); (4) Muscle weight: SCI < TANES, EA (p<0.05); (5) CSA: SCI < TANES, EA (p<0.05)
Zhou L 2017 [30]	In vivo	China	Total n = 60; Sham-OP (10); Model (10); BYHWT-low (10); BYHWT-middle (10); BYHWT-high (10); MCB (10)	Peroneal nerve injury rat model (SD rat, n r, M)	10d / 21d	(1) NF-κB p65, MuRF1 gene expression in 10day; (2) NF-κB p65, MuRF1 gene expression in 21day	BYHWT: Buyang Huanwu Tang; (i) low: 3g/kg/day; (ii) middle: 6g/kg/day; (iii) high: 12g/kg/day; MCB: Mecobalamin 500μg/day	(1) NF-κB p65: Model > BYHWT-low > B-middle (p<0.05) > MCB > B-high (p<0.01 vs. model); MuRF1: Model > BYHWT-low > B-middle (p<0.05) > B-high > MCB (p<0.01 vs. model); (2) NF-κB p65: Model > BYHWT-low > B-middle (p<0.05) > MCB > B-high (p<0.01 vs. model); MuRF1: Model > BYHWT-low > B-middle (p<0.05) > B-high > MCB (p<0.01 vs. model)
Cao R 2017 [31]	In vivo	China	Total n = 63; Sham-OP; Model; EA; groups divided into 7days, 14days, 21days each	Sciatic nerve injury rat model (SD rat, 2 mo, M)	7d / 14d / 21d	(1) Muscle cell apoptosis; (2) Apoptotic factor	EA: Electro-acupuncture at ST36 and BL57; 5Hz, 1.5mA for 10min; once a day for 7d, 14d, 21d	(1) Cell apoptosis (7d, 14d, 21d): Model > EA (p<0.05); (2) Bcl-2↑, Bax↓, Cyto-C↓, Caspase-3↓ in 14d, 21d (p<0.05 vs. Model)

n r: not reported.