TABLE 3.
Summary of metanalysis of Poly herbal combinations used in animal-based models of Metabolic syndrome.
| S. No | Polyherbal combination | Model/animal/treatment duration | Parameters assessed: 5 = glucose/FBG, TG, HDL-C, BP and central obesity (weight, BMI, HC and WC). Parameters met: BMI [WC, HC], BP, HDL, TG, FBG. Additional: TC, LDL | Other parameters related to MetS | Score of study MetS parameters assessed >3 = 1; ≤3 = 0 | Score for effects (3/5: Good) = score 1; <3/5 (not so good) = score 0 | Concentration given | Quality control | Chemical classification | References |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Curcuma longa, Salacia reticulate, Gymnema sylvestre, Emblica officinalis, Terminalia chebula | High fructose diet/Wistar rats/3 weeks | Assessed: 5/5 = Body weight, abdominal waist, BP, glucose, TG, HDL-C, TC, LDL and VLDL. Met: 5/5 = Lowered Body weight, abdominal waist and BMI, reduced BP, AI, improved FBG and OGTT, reduced TG, increased HDL-C. Also, TC, LDL and VLDL reduced | Reduced SGOT, SGPT, Uric acid, MDA. Reduced gastrocnemius muscle weight and fat pads. Reduced infiltration of inflammatory cells and fat accumulation in liver and pancreas | 1 | 1 | Yes | No (Purchased from registered company (References no: SR/KN/CL/1/2003) | No | Thota et al. (2014) |
| 2 | DHSGT: Glycyrrhizae uralensis Fischer (40 g), Rheum undulatum Linne (80 g), Prunus persica Linne (60 g), Cinnamomum cassia Presl (40 g), and Natrii Sulfas (40 g) | HFD-induced obesity/C57BL/6 J mice/7 weeks | Assessed: 5/5 = Body weight, BP, TG, HDL, Glucose. TC and LDL, Met: 5/5 = Reduced body weight (Reduced liver weight and adipose tissue mass, adipocyte size), BP, TG, glucose and increased HDL-c. TC and LDL-c reduced | Decreased serum leptin and leptin mRNA expression. increased mRNA expression of peroxisome proliferator activated receptor-gamma, uncoupling protein-2, and adiponectin in visceral adipose tissue of HFD mice. Inhibition of porcine pancreatic lipase and ACE activities in vitro | 1 | 1 | Yes | No | No | Sung et al. (2014) |
| 3 | Huang-lian-jie-du-tang: Rhizoma coptidis, Radix scutellariae, Cortex phellodendri and Fructus gardeniae (3:2:2:3) | Obese-diet (2% fat, 10% sucrose, 6% salt and 8% defatted milk powder) and drinking water (20% sucrose solution) ad libitum/Wistar male rats/12 weeks | Assessed: 5/5 = BP, body weight, FBG, fasting insulin, and insulin resistance index, TG, HDL-C, LDL-c. Met: 5/5 = Reduction in body weight, BP, FBG, fasting insulin and insulin resistance index, TG levels reduced, and HDL-c increased. LDL-C reduced | inhibited the activation of NF-kB and reduced serine phosphorylation of IRS-1 | 1 | 1 | Yes | Yes | No | Li et al. (2013) |
| 4 | RGPM: Red ginseng and Polygoni Multiflori Radix (1:1) | High fructose/SD rats/6 weeks | Assessed: 5/5 = body weight, Glucose, BP, TG, HDL-c. TC and LDL-c. Met: 5/5 = Reduced body weight and epididymal fat pads weight, reduced TG, systolic BP and increased HDL-c, OGTT improved. TC and LDL-c reduced | reduced leptin, CRP and glutamic-oxaloacetic transaminase, Decreased VCAM-1, ICAM-1, E selectin, MCP-1 and improved PPAR-γ expression. lipid droplets in liver decreased | 1 | 1 | Yes | No (Commercially available product was used) | No | Kho et al. (2016) |
| 5 | Modified lingguizhugan decoction with dietary restriction and exercise. [Poria cocos Wolf, Cinnamomumcassia Presl, Atractylodes lancea DC., Glycyrrhiza uralensis Fisch., Codonopsis pilosula, Nannf. and Rheum palmatum L] (ratio of 12:9:6:6:9:9) | HFD for 12 weeks (30% HFD + dietary restriction ± 45 min swim)/adult SD male rats/1 week after HFD for subsequent 12 weeks | Assessed: 5/5 = body weight, TG, HDL, BP, blood glucose. Met: 5/5 = reduced body weight, TG, BP, blood glucose and insulin levels, Increased HDL. Reduced TC, LDL, adipose and liver tissue weight | Reduced serum FFA, AST, ALT and ALP and TNF-α, leptin in serum and liver | 1 | 1 | Yes | Yes | Yes | Yao et al. (2017b) |
| 6 | Curcuma longa and Nigella sativa | Fructose fed rats (60% fructose in diet + white flour instead of wheat flour) for 6 weeks/SD rats/6 weeks | Assessed: 5/5 = body weight, BP, Fasting serum insulin, FBG, HDL, and TG, Met: 4/5 = Reduced BP, TG, FBG, increased HDL. Reduced LDL, TC and insulin | CRP reduced | 1 | 1 | Yes | No | Yes | Amin et al. (2015a) |
| 7 | Soybean meal and probiotics (Bifidobacterium, longum (BB536) | Obese Zucker rats/Rat/100 days (14.2 weeks) | Assessed: 4/5 = Body weight, TC, TG, HDL and glucose. Met: 4/5 = Reduced weight gain (reduced liver weight and fat), FBG and insulin, TG and Increased HDL. Reduced TC and LDL. | Reduced food intake, ALT, GGT, ALP | 1 | 1 | Yes | No but the diet was purchased commercially | No | Mounts et al. (2015) |
| 8 | ACE: Artemisia iwayomogi and Curcuma longa (1:1) | HFD (10 weeks)/C57BL/6/male mice/10 weeks | Assessed: 4/5 = Body weight, TG, FBG, HDL-C (TC and LDL-c). Met: 4/5 = Reduced body weight (reduced liver weight, epididymal, retroperitoneal, and visceral adipose tissues. Reduced adipocyte size, TC and TG in liver), reduced serum TG, FBG and increased HDL. Reduced LDL-c and TC | PPAR-γ, fatty acid synthase; SREBP-1c; and PPAR-α | 1 | 1 | Yes | Yes | Yes | Lee et al. (2015b) |
| 9 | Fu Fang Zhen Zhu Tiao Zhi formula (FTZ): Ligustrum lucidum W.T. Aiton, fructus; Atractylodes macrocephala Koidz., rhizoma; Salvia miltiorhiza Bunge, radix; Coptis chinensis Franch., rhizoma; Panax notoginseng F.H.Chen, radix; Eucom- mia ulmoides Oliv., cortex; Cirsium japonicum Fisch. ex DC., radix; Citrus medica var. sarcodactylus Swingle, fructus | HFD and insulin resistant HepG2 cell lines/Male SD rats/8 weeks | Assessed: 4/5 = Body weight, FBG, TG, HDL-c, TC. Parameters met: 4/5 = Reduced body weight, FBG (HOMA-IR index), TG increased HDL-c. reduced TC. | Increased PI3K p85 mRNA expression in the adipose tissues. Reduced glucose content, PI3K p85 mRNA and IRS1 protein expression upregulated in insulin resistant HepG2 cells | 1 | 1 | Yes | Yes | Yes | Hu et al. (2014) |
| 10 | Erchen decoction: Pericarpium Citri Reticulatae (9 g), Rhizoma Pinelliae (9 g), Poria (6 g) and Radix Glycyrrhizae (3 g) | HFD for 10 weeks/Male C57BL/6J mice/4 weeks | Assessed: 4/5 = glucose, TG, HDL, obesity, Met: 3/5 = reduced Body weight, Abdominal circumference, FBG and improved OGTT, no effect on insulin levels. Reduced TG but no effect on HDL-c and LDL-c. Reduced TC. | Increased CDKAL1 expression in the liver, visceral and subcutaneous adipose tissues increased, improved islet cell function to secrete more insulin | 1 | 0 | Yes | No | No | Gao et al. (2015) |
| 11 | CPQ: Curcumin, Piperine and Quercetin in a ratio (94 :1:5) | HFD and Low-Dose Streptozotocin (8 weeks)/Albino female Wistar rats/28 days | Assessed: 4/5 = body weight, Glucose, TG, HDL (LDL and TC also assessed), Met: 3/5, improved glucose tolerance, reduced TG and increased HDL. LDL-c and TC reduced | Increased catalase, glutathione, and SOD. Decreased granular degeneration in diabetic liver | 1 | 1 | yes | yes | Yes | Gao et al. (2015) |
| 12 | Extracts of Salvia miltiorrhiza+ Gardenia jasminoides | HFD/SD male rats/4 weeks | Assessed: 4/5 = Body weight, Serum glucose levels, TG, HDL-c (TC, and LDL-C). Met: 3/5 = Reduced serum TC, TG, body weight (reduced visceral fat mass), glucose, enhanced insulin sensitivity. TC and LDL-c reduced | Reduced Serum non-esterified fatty acids, ALT and AST, adipokines, TNF-α and IL-6. Increased leptin in adipose tissue. Enhanced leptin expression | 1 | 0 | Yes | Yes | Yes | Tan et al. (2013) |
| 13 | SUB885C: Fructus Crataegi, Folium Nelumbinis, Folium Apocyni, Flos Rosa rugosae, Radix et Rhizoma Rhei, Depuratum mirabilitum, Thallus Sargassi, and honey fried Radix Glycyrrhizae | ApoE*3Leiden.CETP transgenic mice with mild hypercholesterolemia on semi-synthetic modified Western-type diet (0.2% cholesterol, 15% saturated fat and 40% sucrose; Cell line: 3T3-L1 preadipocyte/Mice/4 weeks | Assessed: 3/5 = Body Weight, TG, HDL-c. also TC, Met: 2/5 = Reduced TG, increased HDL-c. Also reduced TC | Reduced CETP, vLDL-c and TGs. Stimulated lipolysis and inhibited adipogenesis in 3T3-L1 cells | 0 | 0 | Yes | Yes | No | Wei et al. (2012) |
| 14 | Bofu-tsu-shosan formula: Glycyrrhizae radix, Schizonepetae spica, Ephedrae herba, Forsythiae fructus) Others: Platycodi radix, Gypsum fibrosum Atractyloids rhizoma, Rhei rhizoma, Scutellariae radix, Gardeniae fructus, paeoniae radix, cnidii rhizoma, Angelicae radix, Menthae herba, Ledebouriellae radix, Zingilberis rhizoma, Kadinium, Natrium sulfuricum | KKAy mice 9 weeks of age/mice/8 weeks 4.7% BOF (Chronic model), 14 weeks KKAy mice/male mice/5,000 mg/kg BOF dissolved in 1ml of distilled water per 100 g of body weight for 1 day (Acute model) | Assessed: 4/5 = obesity with marked visceral fat, blood glucose, HDL and BP, Met: 2/5 = Lowered Body weight, obesity, BP. LDL reduced. No effect on non-FBG, TC, HDL. | Food intake reduced; White adipose tissue (weight and cell size decreased); expression of genes increased: adiponectin and PPAR receptors; reduction in plasma acylated-ghrelin genes expression (antihypertensive effect) | 1 | 0 | Yes | No, but ingredients were recruited from commercial manufacturers | No | Azushima et al. (2013) |
| 15 | Tang-Nai-Kang: Fructus Ligustri Lucidi, Spica Prunellae vulgaris, Saururus chinensis, Psidium guajava and Radix ginseng (25:10:15:10 | SHR. Cg-Leprcp/NDmcr (SHR/cp) for disease and WKY rats for control/male rat 7 weeks/)/low and high dose 2 weeks | Assessed: 4/5 = BP, sugar, SBP, bodyweight and fat, TG, Met: 4/5 = reduced SBP, body weight and fat mass, FBG, insulin levels. Insulin resistance (OGTT and ITT) was reduced. TC levels did not reduce significantly | AST, ALT, FFA reduced. Gene expression of NAD+ -dependent deacetylase E10 and genes related to fatty acid oxidation were markedly up- regulated in the muscle, liver and adipose tissues | 1 | 1 | Yes | No but the process was carried out by Sichuan Medco Pharmaceutical Limited Corporation (Deyang, China), hence some validation is expected | Yes | Li et al. (2015) |
| 16 | Wendan decoction: Radix Glycyrrhizae (3g), Pericarpium Citri Reticulatae (9g), Poria Cocos (4.5g), Citrus Aurantium (6g), Pinellia, ternata (6g ) and Caulis Bambusae (6g) | High-sugar-fat-diet (15 weeks) and high-fat emulsion (2 weeks)/Wistar male rat/2 weeks | Assessed:3/5 = abdominal perimeters, serum insulin HOMA-IR, HDL. Met: 3/5 = decrease in abdominal perimeters and serum insulin levels, increases in HDL levels, Recovered the HOMA-IR to the control level | pathway analysis and molecular docking simulation | 0 | 1 | Yes | Yes | Yes | Chen et al. (2017) |
| 17 | MCC: Momordica charantia, the pericarpium of Citri reticulate and L-carnitine Dosage: 6 g/kg | HFD/female ICR mice/8 weeks | Assessed: 4/5 = weight gain, FPG and glucose intolerance, insulin sensitivity, TG, HDL (LDL also assessed). Met: 2/5 = reduced TG, FPG, glucose intolerance and Insulin sensitivity index, LDL/HDL ratio and TC levels also reduced | Mitochondrial coupling efficiency of skeletal muscle was improved and reduced carnitine palmitoyl CoA transferase activity | 1 | 0 | Yes | No, but commercial preparation was manufactured and supplied by Infinitus (China) Company Ltd., Guangzhou, China | No | Leong et al. (2013) |
| 18 | SK0506: Gynostemma pentaphyllum, Coptis chinensis and Salvia miltiorrhiza (gypenosides, berberine and tanshinone) | HFD/Male SD rats/4 weeks | Assessed: 3/5 = Body weight, FBG, TG, TC. Parameters met: 3/5 = Lowered body weight, visceral fats, TG, slightly reduced FBG. (Reduced insulin level and NAFA, improved impaired glucose tolerance and glucose infusion rate). TC reduced | Enhanced GLUT4 expression in adipose tissue, enhanced insulin mediated glucose uptake in red quadriceps and white gastrocnemius skeletal muscles, enhanced glycogen synthesis | 0 | 1 | No (but yield is given. It seems all powders were taken in equal ratio) | Yes | Yes | Tan et al. (2011) |
| 19 | Yi Tang Kang: sugar, poria cocos, Atractylodes, radix Astragali, red ginseng and other drugs | MS spleen deficiency syndrome rats with HFD and low dose intraperitoneal injection of streptozocin/Male Wistar rats/10 weeks | Assessed: 4/5 = weight gain, FBG, TG, HDL-c. Met: 3/5 = Reduced FBG and TG and increased HDL-c. Reduced insulin levels, insulin resistance (IR) and lSI | Upregulation of Carboxylesterase and retinal guanylate cyclase 2 precursors. Downregulation of IgG, carnitine acetyltransferase, tubulin beta 5, and Gan Lu sugar binding protein C. protein tyrosine kinase, beta glucosidase | 1 | 1 | No | No | No | Liu and Shi, (2015) |
| 20 | SCH: Pharbitish semen, Trogopterorumh faeces, Cyperih Rhizoma (2:1:1) | HFD mouse model, 3T3-L1and HepG2 cells/Male C57BL/6J/mice/15 weeks | Assessed: 3/5 = Glucose and insulin, TG and TC levels. Parameters met: 3/5 = Reduced glucose levels and insulin levels (HOMA-IR index reduced), Reduced TC and TG. | Regulated adipogenic gene expression, proteins involved in energy metabolism (in maturated 3T3-L1 cells). Increased phosphorylated AMP activated protein, as well as attenuated insulin resistance and hepatic steatosis, improved glucose facilitation by GLUT2 externalization. in FFA-induced steatotic HepG2 cells | 0 | 1 | Yes | No | No | Lim et al. (2019) |
| 21 | Marjoram and chicory Marjoram dry leaves (Origanum majorana) and chicory dry leaves (Cichorium intybus) (1:5 w/v in water) | HFD/female SD albino rats/4 weeks | Parameters assessed: 3/5 = Body weight gain, TG, HDL-c (Additional: TC, LDL-c, VLDL-c, adipose tissue weight). Parameters met: 3/5 = lowered weight gain (Adiposity index and FER), reduced TG, and increased HDL-c; Adipose tissue weight, TC, LDL-c, VLDL-c also reduced | decreased ALT and AST. increased serum free T4 and T3 hormones | 0 | 1 | Yes | No | No | A. Ahmed et al. (2009) |
| 22 | Gambihwan (GBH1): Ephedrae Herba; Coicis semen; Menthae herba Gypsum; Alismatis Rhizoma; Crataegi fructus; Arecae semen; Hordei fructus germinatus GBH2: Ephedrae herba; Coicis semen; Typhae pollen; Castaneae semen; Sinomeni Caulis et Rhizoma; Scutellariae radix | Model: HFD-induced obese mice/C57BL/6 mice (4 weeks old)/8 weeks | Assessed: 4/5 = Body weight Glucose, TG, HDL Met: 2/5 = Reduced body weight, FBG, insulin levels, Improved OGTT. No effect on HDL. Decrease in TC, liver and fat weight | serum inflammatory and hepatic enzyme levels diminished. suppressed lipid accumulation | 1 | 0 | Yes | No | No | Jang et al. (2018) |
| 23 | Sylimarin, Schisandrae Fructus, Crataegus Fructus and Momordica charantia (1:1:1:1) | HFD and Cell lines: 3T3-L1, Caco-2 and HepG2 cell line/C57Bl/6 male mice/8 and 12 weeks | Assessed: 4/5 = body weight (fat pad weight to body weight ratios; liver weight to body weight ratios); TG, glucose, insulin. TC, LDL-c also assessed. Met: 1/5 = reduced diet-induced increase in body weight and fat pad mass, reduced diet-induced increase in liver weight, liver lipid, and plasma lipid. No Effect on glucose and insulin. reduced liver TC and TG. Reduced TC and LDL-c | Improved Plasma adiponectin level, reduced inflammation (reduced mac-3 expression) in liver. Inhibitory effects on 3T3-L1 preadipocytes differentiation inhibited the glucose uptake Inhibited fatty acid uptake prevented the cholesterol uptake | 0 | 0 | Yes | Yes | Yes | Wat et al. (2018) |
| 24 | Herbal Complex extract: Dioscorea Rhizoma, Glycine soja Sieb. et Zucc, Bombycis corpus, Fermented Glycine soja | HFD-low dose STZ-induced diabetes/Rat/- | Assessed: 2/5 = Body weight, food intake and food efficiency ratio, FBG, OGTT. Met: 2/5 = Decrease body weight, improved OGTT and reduced FBG | invitro assay: α-glucosidase inhibition (antidiabetic mechanism); protein tyrosine phosphatase 1β (antidiabetic and antiobesity mechanism) | 0 | 0 | Yes | Not known (Korean language) | Yes | Park et al. (2009) |
Abbreviations: 24hTP, 24 h total urinary protein; 2hPPG, 2 h post prandial glucose; AST, aspartate aminotransferase; ALT, alanine transaminase; ALP, Alkaline phosphatase; BP, blood pressure; BMI, body mass index; CDKAL, CDK5 Regulatory Subunit Associated Protein 1 Like 1); CETP, cholesteryl ester transfer protein; CRP, C-reactive protein; FBG, fasting blood glucose; FFA, free fatty acid; GLUT-4, glucose transporter 4; GGT, glutamyl-transferase; HC, hip circumference; HDL-C, high density lipoproteins; HFD, high fat diet; HOMA-IR, homeostatic model assessment for insulin resistance; ICAM-1, intercellular adhesion molecules; IRS-1, Insulin receptor substrate 1; KKAy, cross between diabetic KK and lethal yellow; LDL, low density lipoprotein; Monocyte chemoattractant protein-1; MAU/MA, microalbuminuria; MDA, malondialdehyde; NAFA, non-esterified fatty acids; NF-kB, Nuclear Factor kappa-light-chain-enhancer of activated B cells; PI3K Phosphoinositide 3-kinase SREBP, sterol regulatory element-binding transcription factor; PPAR-γ/a, Peroxisome proliferator-activated receptor gamma/alpha; SD Rats: Sprague Dawley rats; SGOT: Serum glutamic oxaloacetic transaminase; SGPT: Serum glutamic pyruvic transaminase; SOD, superoxide dismutase; TC, total cholesterol; TG, triglycerides; TNF, Tumor necrosis factor; vLDL, very low density lipoprotein; UACR, urea creatinine albumin ratio; vCAM-I, Vascular cell adhesion molecule 1; WC, waist circumference; WHR, waist hip ratio; WKy, Wistar Kyoto.