Table 2.
HS effects on inflammation biomarkers in included studies.
| S/N | First Author, year | Experimental Model | HS formulation | Dosage/route | Inflammatory mediator investigated | Tissue Examined | Sample size (n) (*) | Methodological Instrumentation | Major findings | Reference |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Fakeye, (2008) | Healthy Mice | Aqueous and ethanol Extract of HS | 300 mg/kg body weight, oral administration for 28 days | IL-10, TNF- α | Serum | 10 | ELISA | IL-10 (-) (#3) | (41) |
| TNF- α (↓)(#3) | ||||||||||
| 2 | Nurkhasanah (2015) | DMBA treated rats () | Ethanol extract | 10 (mg/kg body weight) oral administration for 21 days before toxicity induction with DMBA | IL-10, IL-14 | Spleen | not stated | immunohistochemistry | IL-10 (↑) | (39) |
| IL-14 (↑) | ||||||||||
| 3 | Villalpando-Arteaga (2013) | High fat diet induced obese mice | Aqueous Extract (room temperature) | 33 mg anthocyanin equivalent per kg. Administration of HS was done thrice weekly for 8 weeks using an orogastric-way. | IL-1β, IL-6, IL-10, TNF- α | Liver | 10 | PCR | IL-6 (-) | (9) |
| IL-10 (-) | ||||||||||
| TNF- α (↓) | ||||||||||
| IL-1β (↓) | ||||||||||
| 4 | Wang (2011) | STZ-induced Diabetic rats | Aqueous Extract 100°C | 100 mg/kg body weight, fed orally to the animals for 8 weeks after which diabetes was induced by STZ injection | NF-κB | Liver | 10 | Electrophoretic Mobility Shift Assay (EMSA) | Up regulated expression of NF-κB | (37) |
| 5 | Kao (2009) | Rats challenged with LPS | Methanol/ethyl acetate extract | 20 mg/kg body weight oral administration for 5 days. | Cyclooxygenase-2 | Liver | 10 | Western blotting/Chemiluminescence | Down regulated Cyclooxygenase-2 expression | (38) |
| 6 | BeltranDeb´on (2010) | Healthy Human | Aqueous Extract (100°C) | 10 g administered orally 3 hours before study. | IL-8, IL-6, MCP-1 | Blood Plasma | 10 | multiplex cytometric bead-based assay | IL-6 (nd) | (20) |
| IL-8 (nd) | ||||||||||
| MCP-1 (↓) | ||||||||||
| 7 | Beltran-Deb´on (2015) | Healthy Human | Aqueous Extract | 5g of extract (569 mg of polyphenol) was administered orally for 3 hours before-study | IL-6, IL-8, CRP protein, ACE, TNF-α | Blood Serum | 10 | ELISA | IL6 (-) (#1) | (47) |
| hs-CRP kit from Biokit. | IL8 (-) (#1) | |||||||||
| CRP (-) (#1) | ||||||||||
| ACE (↓) (#1) | ||||||||||
| 8 | Herrera-Arelano (2007) | Hypertensive Human | Aqueous extract (60°C) | 250 mg anthocyanin administered orally for 4 weeks. | ACE | serum | 171 | HPLC/Chromolite Column | ACE (↓) | (24) |
| 9 | Ali (2019) | Rat model of myocardial infarction | Aqueous extract | 100 mg/kg body weight administered orally for 7days | IL-6, IL-10 | Plasma/Heart | 12 | ELISA | IL-6 (↓) | (44) |
| IL 10 (↓) | ||||||||||
| 10 | Bayani (2018) | Over trained Rat | Ethanol Extract | 500 mg/kg body weight administered orally shortly before overtraining for 11 weeks | IL-1β | Plasma, Hippocampus | 10 | ELISA | IL-1β Plasma (-) | (52) |
| IL-1β Hippocampus (-) | ||||||||||
| 11 | Sogo (2015) | LPS-induced inflammation in Mouse | Delphinidin | Intraperitoneal administration of 15 µMl/kg body weight for 4 days before LPS treatment | TNF-α, IL-6, MCP-1, Paw edema | Serum, paw | 8 | ELISA | TNF-α (↓) | (11) |
| 3-sambubioside and Delphinidin | IL-6 (↓) | |||||||||
| Purified from HS | MCP-1 (↓) | |||||||||
| Paw edema (↓) | ||||||||||
| 12 | Chou (2016) | LPS-induced inflammation in Mouse | Aqueous extract (4°C) | 200 mg/kg body weight orally administered for 7days before LPS treatment | Il12b,Il15,Il17ra,Il17c,Il1β,Il1rap,Il6,Il22,Ifitm10, Ifi47,Ifnb1,Igtp,Iigp1,Irf1,Irf8, Ccrl2 Cxcl11,Cxcl2,Cxcl9,Ccl12,Ccl22,TNF-α, Tnfsf10, Tnfsf15,Cox-2 | Kidney | 10 | Microarray | Il12b (↓) | (31) |
| Il15 (↓), | ||||||||||
| Il17ra (↓) | ||||||||||
| Il17c (↓) | ||||||||||
| Il1β (↓)(#2) | ||||||||||
| Il1rap (↓) | ||||||||||
| IL-6 (↓)(#2) | ||||||||||
| IL-22 (↓) | ||||||||||
| Ifitm10 (↓) | ||||||||||
| Ifi47 (↓) | ||||||||||
| Ifnb1 (↓) | ||||||||||
| Igtp (↓) | ||||||||||
| Iigp1 (↓) | ||||||||||
| Irf1 (↓), | ||||||||||
| Irf8 (↓) | ||||||||||
| Ccrl2 (↓) | ||||||||||
| Cxcl11 (↓) | ||||||||||
| Cxcl2 (↓) | ||||||||||
| Cxcl9 (↓) | ||||||||||
| Ccl12 (↓) | ||||||||||
| Ccl22 (↓) | ||||||||||
| TNF-α (↓)(#2) | ||||||||||
| Tnfsf10 (↓) | ||||||||||
| Tnfsf15 (↓) | ||||||||||
| Cox-2 (↓) | ||||||||||
| iNOS2 (↓)(#2) | ||||||||||
| NF-κB (P56) (↓) | ||||||||||
| 13 | Abdel-Rahman (2017) | L-NAME- induced hypertensive rats | Hydro-alcoholic extract of Hibiscus | 250 mg/kg body weight administered orally alongside with L-NAME for 4weeks. | ACE | Blood serum | 14 | ELISA kit | ACE (↓) | (25) |
| sabdariffa and Oleaeuropaea in a ratio 2:1 respectively. | ||||||||||
| 14 | Ezzat (2016) | TAA-induced hepatotoxic rats | Trifluoroacetic acid extract of HS | 100 mg/kg body weight administered orally for 5 days per week for four weeks. | TNF-α, IL-6, IFN-γ, NF-κB | Blood serum | 16 | ELISA kit | TNF-α (↓) | (17) |
| IL-6 (↓) | ||||||||||
| IFN-γ (↓) | ||||||||||
| NF-κB (↓) | ||||||||||
| 15 | Asgary (2016) | Human subject with metabolic syndrome | Encapsulated powdered HS | 500 mg of encapsulate HS (3 mg anthocyanin equivalent) oral administration for 4weeks. | hs-CRP | Serum | 113 | Not stated | hs-CRP (-) | (50) |
| 16 | Joven (2014) | Human subjects with metabolic syndrome | Polyphenol Extract from HS | 125 mg/kg of HSE was administered orally twice daily for 4 weeks | 2-microglobulin,ACE,CCL2, hsCRP, IL-1β, IL-6, IL-8, TNF-α | Serum | 31 | ELISA, AutoAnalyser | CRP (–) (#1) | (42) |
| IL-6 (↓) (#1) | ||||||||||
| ACE (-) (#1) | ||||||||||
| CCL2 (↓) (#1) | ||||||||||
| IL-1β (↓) (#1) | ||||||||||
| IL-8 (↓) (#1) | ||||||||||
| TNF-α (↓) (#1) | ||||||||||
| 2-microglobulin (-) (#1) | ||||||||||
| 17 | Abubakar (2019) | Men with low risk of cardiovascular-disease | Aqueous extract (100°C) | One time oral administration of 7.5 g of HS extract (containing 150 mg total anthocyanins and 311mg gallic acid) | CRP | plasma | 22 | AutoAnalyser | CRP (-) | (51) |
| 18 | Santoso (2019) | Over-trained Wistar Rat | Methanolic calyx extract | 500 mg/kg body weight administered orally shortly before overtraining for 11 weeks | IL-6, TNF-α | Heart | 10 | ELISA | TNF-α (↓) | (43) |
| IL-6 (↓) | ||||||||||
| 19 | Nurfaradilla (2019) | Hypertensive Rat (2K1C model of hypertension) | Aqueous Extract (50°C) | 150 mg/Kg body weight, administered orally for two weeks | Serum ACE, Plasma Ang II. | Plasma/ serum | 12 | Spectrophotometry UV-Vis, ELISA | ACE (↓) | (26) |
| Angiotensin II (↓) | ||||||||||
| 20 | Huang (2016) | HFD and STZ-induced diabetic rat model | Polyphenolic extract from HS | 200 mg/kg body weight was orally administered along side HFD for seven weeks before STZ injection | AT1 receptor | Kidney | 16 | Radioimmunoprecipitation assay | AT1 receptor (↓) | (46) |
| 21 | Diez-Echave (2020) | HFD-induced obesity mice | Aqueous extract of HS | Oral administration for 42 days at 1, 10, 25 mg/kg body weight | TNF-alpha, IL-1β, IL-6, MCP-1, TLR4 | Liver Adipose | 20 | RT-qPCR | TNF-alpha (↓) | (16) |
| IL-1β (↓) | ||||||||||
| IL-6 (↓) | ||||||||||
| MCP-1 (↓) | ||||||||||
| TLR4 (↓) | ||||||||||
| 22 | Perez-Torres (2013) | Sucrose induced Metabolic syndrome rat model | Aqueous Extract (100°C) | Unclear dosage and route, 24 weeks treatment. | iNOS | Liver | 14 | immunoblotting | iNOS (↓) | (45) |
| 23 | Tseng (1998) | TPA induced mouse ear edema model | Protocatechuic acid extract of HS | 10 or 20umol applied on the skin twice daily for 4 days. | Ear edema | Ear | 15 | Gravimetric | Ear edema (↓) | (49) |
| 24 | Nwachukwu (2015) | Mild to moderate essential hypertensive humans | Aqueous Extract (100°C) | Oral administration of 150mg/kg body weight/day, for 4 weeks | ACE | Serum | 50 | HPLC | ACE(-) | (14) |
| 25 | Dafallah (1996) | Carrageenan induced paw edema rat model | Aqueous Extract (room temperature) | 500 mg/kg body weight orally administered 3 hours before carrageenan injection | Paw Edema | Paw | 12 | Water Displacement method | Paw Edema (-) | (53) |
| 26 | Lubis (2020) | dextran sodium sulfate-induced colitis mice model | Ethanol extract | 300 mg/kg body weight/day administered orally for 28 days | IL-6 and TNF-α, IL-10, HCIS. | Colon | 11 | Histopathology and Immunohistochemistry | IL-6 (↓) | (40) |
| TNF-α (↓) | ||||||||||
| IL-10 (↑) | ||||||||||
| HCIS (↓) | ||||||||||
| 27 | Ali (2011) | Xylene-induced ear edema mice model | Ethanol extract | A one-time oral HS administration at 250 and 500 mg/kg body weight | Ear edema | Ear | 15 | Gravimetric | Ear edema (↓) | (1) |
(*) sample size used for control and test group.
(nd) not detected.
(↓) shows significant decrease of inflammatory mediator.
(↑) shows significant increase of the inflammatory mediator.
(-) shows insignificant difference between the treated and untreated groups.
(#1) The SD value used for meta-analysis was estimated using Revman5.3.
(#2) The data reported in Table 2 of Chou et al. (31) was transformed for meta-analysis using the formula below, . where EU is the transformed data for the exposed-untreated group, LPS is the data reported for LPS exposed, and LPSroselle is the data reported for the treated group. ET is the transformed data for the exposed and treated group.
(#3) The individual outcomes reported in Tables 1 and 2 of Fakeye et al. (41) were used to generate a mean and SD value that was used for the meta-analysis.
2K1C, Two-kidney-one-clip; ACE, Angiotensin-converting enzyme; Ang II, Angiotensin II; AT1 receptor, Angiotensin II type 1 receptor; Colitis Inflammation Score; CRP, C-reactive protein; DMBA, Dimethylbenz(A)Anthracene; ELISA, Enzyme-linked immunosorbent assay; HCIS, Histological; HFD, High fat diet; HPLC, High Performance Liquid Chromatography; HS, Hibiscus sabdariffa; hs-CRP, High-sensitivity C-reactive protein; IFN-γ, Interferon-γ; IL-10, Interleukin 10; IL-14, Interleukin 14; IL-1β, Interleukin 1β; IL-6, Interleukin 6; IL-8, Interleukin 8; iNOS, inducible Nitric Oxide synthase; L-NAME, N(G)-nito-L-arginine-methyl ester; LPS, Lipopolysaccharides; MCP-1/CCL2, Monocyte Chemoattractant Protein-1; NF-κB, nuclear factor kappa B; PCR, Polymerase chain reaction; RT-qPCR, Quantitative reverse transcription PCR; STZ, Streptozotocin; TAA, Thioacetamide; TLR4, Toll-like receptor 4; TNF-α, Tumor necrosis factor; TPA, 12-O-tetradecanoylphorbol-13-acetate.