Table 3.
Biological properties of extracts or compounds from Abelmoschus manihot L. and their possible mechanisms of action observed in the literature.
| Biological activity | Extract/compound | Type | Testing subject | Dose and duration | Mechanisms/effects | Reference |
|---|---|---|---|---|---|---|
| Antidiabetic nephropathy activity | HKC | In vivo | Doxorubicin-induced nephropathy in rat | 0.5 and 2.0 g/kg, i.g., for 28 days | TNF-α, TGF-β1, p-p38MAPK protein expression ↓; infiltrated ED1+ and ED3+ macrophages ↓ | Tu et al., 2013 |
| HKC | In vivo | Unilateral nephrectomy combined STZ-induced DN in rat | 0.75 and 2.0 g/kg, i.g., for 56 days | p38MAPK, p-Akt, TGF-β1, TNF-α protein expression ↓; BUN, UA, BW, Alb levels ↓ | Mao et al., 2015 | |
| HKC | In vivo | STZ-induced DN in rat | 75, 135, and 300 mg/kg, i.g., for 84 days | PPAR, CD36, and LPL mRNA ↑; Alb, triglyceride, cholesterol, fat, TNF-α, IL-6, IL-1, and IL-2 levels ↓ | Ge et al., 2016 | |
| HKC | In vitro | HRMC cells | 5 mg/mL | PPAR activities↑; lipoprotein lipase, fatty acid synthase, aP2, and GLUT4 mRNA expression ↑ | Ge et al., 2016 | |
| HKC | In vitro | HepG2 cells | 5 mg/mL | CD36, CPT1, PDK4, and ACO mRNA expression ↑ | Ge et al., 2016 | |
| HKC | In vivo | Adenine-induced CRF in rats | 0.75 g/kg, i.g., for 28 days | Scr, BUN, and UP levels ↓; α-SMA, p-ERK1/2, and NOX-1/2/4 protein expression ↓ | Cai et al., 2017a | |
| HKC | In vitro | High glucose-induced EMT in HK-2 cells | 100 µM | α-SMA, p-ERK1/2, NOX-1, NOX-2, and NOX-3 protein expression ↓ | Cai et al., 2017a | |
| HKC | In vivo | STZ-induced DN in rat | 2 g/kg, i.g., for 28 days | p-Akt, p-mTOR, p-p70S6K, and TGF-β1 protein expression ↓ | Wu et al., 2018 | |
| Hyperoside | In vitro | High glucose-induced in mesangial cells | 5 and 15 µg/mL | PI3K, Akt, mTOR, and p70S6K protein expression ↓ | Wu et al., 2018 | |
| Hyperoside | In vivo | IR-induced AKI in mice | 20 mg/kg, i.p. | BUN, Scr, apoptosis, and caspase-3 ↓; DHE fluorescence ↑; OMA1 ↑; OPA1 ↓ | Wu L. et al., 2019 | |
| Hyperoside | In vitro | CoCl2-induced HK-2 cells | 50, 100, 150, and 200 µM | Apoptosis, and caspase-3 ↓; ROS levels ↓; OMA1 ↑; OPA1 ↓ | Wu L. et al., 2019 | |
| Hyperoside | In vitro | Podocyte induced by AGE | 50 and 200 µg/mL | Podocyte apoptosis ↓; caspase-3/8 protein expressions ↓ | Zhou et al., 2012 | |
| TFAM | In vivo | STZ-induced DN rats | 0.2 g/kg, i.g., for 168 days | Ratio of urinary microalbumin/creatinine↓; 24 h urinary total protein ↓ | Zhou et al., 2012 | |
| TFAM | In vitro | HRMC and HK-2 cell lines induced by AGE | 20 µM | iRhom2/TACE signaling ↓ | Liu et al., 2018 | |
| TFAM | In vivo | Unilateral nephrectomy combined STZ-induced DN in rat | 0.075, 0.135, and 0.3 g/kg, i.g., for 84 days | Scr, BUN levels ↓; IL-1, IL-2, IL-6, and TNF-α expressions ↓; iRhom2/TACE signaling ↓ | Liu et al., 2018 | |
| TEA | In vivo | Doxorubicin-induced nephropathy in rat | 0.2 g/kg, i.g., for 168 days | Proteinuria, albumin, ROS-ERK1/2-NLRP3 inflammasome protein activation ↓; caspases 3/8 ↓ |
Li et al., 2019 | |
| TEA | In vitro | Doxorubicin-induced NRK-52E cells | 100 µg/mL | P38 and ERK1/2 signaling pathway ↓ | Li et al., 2019 | |
| Aqueous extract | In vivo | High-fat diet and STZ-induced DN mice | 0.1 g/kg, i.g., for 35 days | pCr, BUN, and urinary albumin levels ↓ | Kim et al., 2018 | |
| Antioxidant and antiadipogenic activity | Floramanosides A–F | In vitro | DPPH scavenging activity | 0–200 µM | DPPH scavenging activity with SC50 of 10.1, 6.2, 10.4, 12.5, 24.0, and 25.1 µm, respectively | Zhang et al., 2013 |
| Floramanosides A–F | In vitro | AR inhibitory activity | 0–200 μM | AR inhibition activity with IC50 of 17.8, 13.7, 7.1, 2.2, and 8.3 µm, respectively | Zhang et al., 2013 | |
| TFAM | In vitro | DPPH scavenging activity | 25, 50, 100, and 200 µg/mL | DPPH scavenging activity with IC50 of 0.288 mg/mL | Li et al., 2016 | |
| TFAM | In vitro | 3T3-L1 cells | 25, 50, 100, and 200 µg/mL | PPARγ and C/EBPα mRNA expression ↓ | Li et al., 2016 | |
| TFAM | In vivo | D-gal-induced mouse model | 40, 80, and 160 mg/kg, i.g., for 42 days | CAT, GPx, SOD, and T-AOC activities ↑; MDA, TNF-α, and IL-1β level ↓; Nrf2, HO-1 and NQO1 protein expression ↑; GPx, SOD, and CAT mRNA expression ↑ | Qiu et al., 2017 | |
| Anti-inflammatory and analgesic activity | Petroleum ether and methanol extracts | In vivo | Carrageenan and histamine-induced paw edema model | 100, 200, and 400 mg/kg, i.g. | Edema volume ↓ | Jain et al., 2009; Jain and Bari, 2010 |
| Ethanol extracts | In vivo | DSS-induced colitis in mice | 0.25, 0.5, and 1.0 mg/g, i.g., for 6 days | IL-1β, IL-6, IL-17, IL-22, TNF-α, CXCL1, CXCL2, CXCL9, CXCL10, CCL-2, Madcam, P-selectin, and E-selectin mRNA expression ↓ | Zhang et al., 2019 | |
| TFAM | In vivo | Acetic acid writhing test in mouse model | 5, 10, and 20 mg/kg, i.p. | Inhibition rate of 57.53%, 42.81%, and 57.19%, respectively | Fan et al., 2003 | |
| TFAM | In vivo | Formalin pain test, and KCl test in mouse model | 140 and 280 mg/kg, i.g. | Phase I and phase II in the formalin pain ↓ | Fan et al., 2003 | |
| Petroleum ether and methanol extracts | In vivo | Tail immersion and hot plate model in mice | 100, 200, and 400 mg/kg, i.g. | Pain threshold ↓ | Pritam et al., 2011 | |
| Anticonvulsant and antidepressant activity | Compounds (19) and (25) | In vivo | TST- and FST-induced mouse model | 15, 30, and 60 mg/kg, i.g., for 1 day | TST, FST ↓; BDNF, TrkB ↑; p-eEF2 ↓ | Cai et al., 2017b |
| TFAM | In vivo | PSD in rats | 25, 50 and 100 mg/kg, i.g., for 24 days | SOD, GSH-Px activities ↑; MDA ↓ | Hao et al., 2007 | |
| TFAM | In vivo | PSD injury in rats | 40, 80, and 160 mg/kg, i.g., for 24 days | SOD, GSH-Px activities ↑; MDA ↓; BDNF and CREB mRNA and protein expressions ↑ | Liu et al., 2009 | |
| Ethanol extract | In vivo | PTZ-induced clonic convulsions and mortality in mice | 100 and 200 mg/kg, i.g. | Survival time↑; mortality rate ↓ | Guo et al., 2011 | |
| Neuroprotective activity | TFAM | In vivo | Acute incomplete cerebral ischemia in rats | 50 and 100 mg/kg, i.g., for 3 days | Incidence of brain edema ↓ | Gao et al., 2003 |
| TFAM | In vitro | Cultured rat hippocampal neurons | 0.2 mg/mL | NMDA receptor desensitization ↑ | Cheng et al., 2006 | |
| Antiviral activity | Hyperoside | In vitro | HepG2.2.15 cells | 0.05 g/L | Inhibition rates of HBeAg and HBsAg were 86.41% and 82.27%, respectively | Wu et al., 2007 |
| Hyperoside | In vivo | DHBV infection duckling model | 0.05 and 0.1 g/kg, i.g., for 10 days | DHBV-DNA levels ↓ | Wu et al., 2007 | |
| Antitumor activity | Polysaccharide | In vitro | SMMC-7721and HepG2; MGC-803 and MKN-45 | 50–400 μg/mL | Antiproliferation | Zheng et al., 2016 |
| HKC | In vivo | Multiple myeloma-prone mouse model | 3.75 g/kg, i.g., 3 times a week | Survival rate ↑ | Hou et al., 2020 | |
| Immunomodulatory activity | Polysaccharide | In vitro | RAW264.7 cells | 50, 100, and 200 μg/mL | TNF-α, IL-6 secretion ↑; spleen lymphocyte proliferation ↑ | Pan et al., 2018 |
| Hepatoprotective activity | TFAM | In vivo | CCl4-induced acute liver damage in mice | 125, 250, and 500 mg/kg, i.g., for 7 days | MDA, ALT, AST, ALP, and γ-GT levels ↓; GSH, GPx, CAT, and GST activities ↑ | Ai et al., 2013 |
| TFAM | In vitro | CCl4-exposed hepatocytes | 9, 18, 36, and 72 mg/L | ALT, AST, and ALP level ↓ | Ai et al., 2013 | |
| TFAM | In vivo | ANIT-induced liver injury in rats | 125, 250, and 500 mg/kg, i.g., for 9 days | ALT, AST, LDH, ALP, GGT, TBIL, DBIL, and TBA levels ↓; MDA, TNF-α, and NO contents ↓; SOD, GSH, and GST activities ↑; BSEP, MRP2, and NTCP mRNA expression ↑ | Yan et al., 2015 | |
| Cardioprotective activity | TFAM | In vivo | Myocardial ischemia–reperfusion injury in rats | 100 and 200 mg/kg, i.p. | MDA, CPK, LDH ↓; SOD activity ↑; apoptotic cells ↓; Bcl-2 expression ↑ | Li et al., 2006 |
| TFAM | In vivo | Myocardial ischemia–reperfusion in rabbits | 4, 8, and 16 mg/kg, i.v. | SOD, GSH-Px activities ↑; MDA level ↓; ICAM-1 mRNA expression ↓ | Fan et al., 2006 | |
| TFAM | In vivo | Myocardial ischemia–reperfusion in rats | 40 and 80 mg/kg, i.g. | CK, LDH, IL-6, IL-1β, and TNF-α levels ↓; SOD activity ↑; MDA content ↓ | Lv et al., 2017 | |
| Proangiogenic activity | TFAM | In vitro | HUVECs | 5, 10, and 20 μg/mL | Induced the HUVECs proliferation, migration, invasion, and tube formation; VEGF-A, VEGFR2, PI3K, and Akt protein expressions ↑ | Zhu et al., 2018 |
| TFAM | In vivo | Chick CAM model | 0, 5, 10, and 20 μg/mL | Promoted the formation of blood vessels | Zhu et al., 2018 | |
| Effect on cerebral infarction | TFAM | In vivo | Nitrogen anoxia model in mice | 30, 60, and 120 mg/kg, i.v. | Survive time ↑; MDA content ↓ | Guo and Chen, 2002 |
| TFAM | In vivo | Cerebral ischemia–reperfusion in rabbits | 12, 24, and 48 mg/kg, i.v. | EEG, MDA, and LDH levels ↓ | Guo and Chen, 2002 | |
| TFAM | In vivo | MCA rat model | 25, 50, and 100 mg/kg, i.g. | Cerebral infarction weight ↓; LDH and NO ↑ | Gao et al., 2002 | |
| TFAM | In vivo | MCA rat model | 20, 40, 80, and 160 mg/kg, i.g. | Cerebral infarction size ↓; LDH, MDA ↓; iNOS mRNA expression ↑ | Wen and Chen, 2007 | |
| Anti-Crohn’s disease activity | TFAM | In vitro | TGF-β1-induced EMT in IEC-6 cells | 5, 10, and 15 µg/mL | Ecadherin and ZO1 mRNA and protein expressions ↑; vimentin, Ncadherin, Smad 2/3, pp38, pJNK and pERK1/2 mRNA and protein ↓ | Yang B. L. et al., 2018 |
| Effect on bone loss | A. manihot leaves | In vivo | Ovariectomized rats | 15% of leaves of in the diet | BMD and BMC ↑ | Puel et al., 2005 |
| Antiplatelet activity | TFAM | In vivo | Rat models induced by artery–vein bypassing thrombus formation | 25, 50, and 100 mg/kg, i.g., for 3 days | Thrombus weight ↓ | Guo et al., 2005 |
| TFAM | In vitro | Collagen-induced platelet aggregation in rabbits | 0.025, 0.05, 0.10 mg/mL | Resting ↓; free intracellular calcium concentration ↑ | Guo et al., 2005 | |
| Other activity | Hyperoside | In vivo | Ethylene glycol-fed rats | 20 mg/kg, i.g., for 21 days | Crystal deposit numbers ↓; SOD, CAT activities ↑ | Zhu et al., 2014 |
AKI, acute kidney injury; AR, aldose reductase; CAM, chorioallantoic membrane; CRF, chronic renal failure; EMT, epithelial-mesenchymal transition; MCA, middle cerebral artery; PSD, poststroke depression; ACO, acyl-CoA oxidase; AGE, dvanced glycation end-products; Akt, serinethreonine kinase; Alb, albumin; ALP, alkaline phosphatase; ALT, alanine aminotransferase; ANIT, α-naphthylisothiocyanate; aP2, adipose fatty acidbinding protein; AST, aspartate aminotransferase; BDNF, brain-derived neurotrophic factor; BMC, bone mineral content; BMD, bone mineral density; BSEP, bile salt export pump; BUN, blood urea nitrogen; BW, body weight; CAT, catalase; CK, creatinine kinase; CPK, creatine phosphokinase; CREB, cAMP-response element-binding protein; DBIL, direct bilirubin; DHBV, duck hepatitis B virus; DHBV-DNA, duck hepatitis B virus-DNA; DHE, dihydroethidium; DN, diabetic nephropathy; DPPH, 1,1-diphenyl-2-picrylhydrazyl; DSS, dextran sulfate sodium; ED, macrophage; EEG, electroencephalography; EMT, pithelial-mesenchymal transition; FST, forced swimming test; GGT, gamma-glutamyltransferase; GLUT4, glucose transporter-4; GPx, glutathione peroxidase; GSH, glutathione; GSH-Px, glutathione-Px; GST, glutathione transferase; HBeAg, hepatitis Be antigen; HBsAg, hepatitis B surface antigen; HKC, Huangkui capsule; HO-1, heme oxygenase-1; HRMC, human renal mesangial cells; HUVEC, human umbilical vein endothelial cells; i.g., intragastrically; i.p., intraperitoneally; IC50, 50% inhibitory concentration; ICAM, intercellular cell adhesion molecule; IL, interleukin; iNOS, nitric oxide synthase; IR, ischemia/reperfusion; LDH, lactate dehydrogenase; LPL, lipoprotein lipase; MAPK, mitogen-activated protein kinase; MDA, malondialdehyde; MRP2, multidrug resistance-associated protein 2; NMDA, N-methyl-D-aspartic acid; NQO1, NAD(P)H: quinoneoxidoreductase NQO1:EC1.6.99.2; Nrf2, nuclear factor(erythroid-derived2)-like 2 protein; NTCP, Na+-taurocholate cotransporting polypeptide; OMA1, metalloendopeptidase OMA1; OPA1, optic atrophy 1; pCr, plasma creatinine; PI3K, phosphatidylinositol-3-kinase; PPAR, peroxisome proliferator-activated receptors; PTZ, pentylenetetrazole; ROS, reactive oxygen species; SC50, 50% scavenging concentration; Scr, serum creatinine; SMA, a-smooth muscle actin; SOD, superoxide dismutase; STZ, streptozotocin; TACE, tumor necrosis factor-a converting enzyme; T-AOC, total antioxidant capacity; TBA, total bile acid; TBIL, total bilirubin; TEA, total extracts of A. manihot flower; TFAM, total flavones of A. manihot; TGF, transforming growth factor-β1; TNF, tumor necrosis factor; TrkB, tyrosine receptor kinase; TST, tail suspension test; UA, serum uric acid; UP, urine protein; VEGF-A, vascular endothelial growth factor-A; VEGFR2, VEGF receptor-2; γ-GT, gamma glutamyltransferase.