TABLE 1.
Bioactivities of the main components extracted from C. officinalis.
| Components | Bioactivities | Diseases/Tissues | Targets (In vitro and In vivo) | Effects | References |
|---|---|---|---|---|---|
| Morroniside | Anti- inflammation | Osteoarthritis | In vitro: IL-1β treated primary mouse chondrocytes; in vivo: destabilization of the medial meniscus-treated C57BL/6J mice. | Inhibit NF-κB signaling and proinflammatory NLRP3 expression; down-regulate the expressions of MMP-13 and caspase-1; promote collagen type II and cartilage matrix synthesis. | (Yu et al., 2021) |
| Colitis | In vitro: LPS treated colorectal cancer cell; in vivo: DSS induced acute colitis mouse model. | Increase the expression of tight junction proteins; decrease the expressions of pro-inflammatory cytokines; suppress the phosphorylation of STAT3 and NF-κB. | (Yuan et al., 2020) | ||
| Anti-oxidation | Neuropathic pain | In vitro: H2O2 treated microglial N9 cells, HEK293 cells and HEK293T cells; in vivo: neuropathic pain rat model (L5, L6 spinal nerves ligation). | Active GLP-1 receptors. | (Xu et al., 2017) | |
| Anti-apoptosis | Diabetic cardiomyopathy | In vitro: primary cultured rat cardiomyocytes. | Down-regulate the expressions of ROS, caspase-3 and bax; up-regulate the expression of bcl-2. | (Pi et al., 2017) | |
| Anti-diabetes | Diabetic osteoporosis | In vitro: primary cultured rat BMSCs; in vivo: DM rats model (single intraperitoneal injection of 60 mg/kg STZ, SD rats). | Promote osteogenic differentiation of BMSCs; up-regulate the activation and expression of Glo1; down-regulate AGEs formation and RAGE expression. | (Sun et al., 2020) | |
| Renal tissue | In vitro: AGEs treated mesangial cells. | Inhibit the secretion of ECM major components (LN, FN, and Col-IV) induced by AGEs; inhibit the expressions of RAGE, p38MAPK, NF-κB, and TGF-β induced by AGEs. | (Lv et al., 2016b) | ||
| Liver | In vitro: serum-free DMEM with 50mmol/L glucose treated HepG2 cells; in vivo: DM mice model (single intraperitoneal injection of 60 mg/kg STZ). | Promote glucose uptake; decrease FBG levels in DM mice. | (He et al., 2016) | ||
| Liver | In vivo: db/db mice. | Decrease serum glucose; decrease ROS and lipid peroxidation in liver tissue; down-regulate the expressions of NOX4, P22phox, SREBP-1, SREBP-2, Nrf2, HO-1, NF-κB, COX-2, iNOS, MCP-1, bax and Cytochrome C in liver tissue; up-regulate GSH/GSSG ratio. | (Park et al., 2011a; Park et al., 2009) | ||
| Renal tissue | In vivo: db/db mice; STZ (50 mg/kg)-induced DM rats. | Decrease serum TC; decrease renal lipid peroxidation and ROS levels; down-regulate renal SREBP-1, SREBP-2, NF-κB, COX-2 and iNOS expressions; up-regulate GSH/GSSG ratio. | (Park et al., 2010b; Yokozawa et al., 2010) | ||
| Renal tissue | In vivo: STZ (50 mg/kg)-induced DM rats. | Decrease serum glucose, BUN and urinary protein levels; elevate serum albumin and total protein; reduce glycosylated protein and lipid peroxidation; down-regulate RAGE, HO-1. | (Yokozawa et al., 2008) | ||
| Renal tissue | In vitro: AGEs treated rat mesangial cells. | Inhibit AGE-induced mesangial cells proliferation and cell cycle; down-regulate ROS and MDA; up-regulate SOD and GSH. | (Xu et al., 2006) | ||
| 1,6-α-glucans | Anti-atherosclerosis | Atherosclerosis | In vitro: oxidized-LDL treated RAW264.7 macrophages; in vivo: ApoE−/− mice fed with HFD. | Reduce ox-LDL induced cholesterol levels and inhibit the foam cell formation in RAW264.7 cells; reduce aortic atherosclerotic lesion area in ApoE−/− mice fed with HFD; decrease serum LDL, TC levels, MDA activity, and CD36, SR-A1 expressions; increase SOD activity. | (Zhang et al., 2020) |
| Loganin | Anti- inflammation | Colitis | In vitro: LPS treated colorectal cancer cell; in vivo: DSS-induced acute colitis mouse model. | Increase the expression of tight junction proteins; decrease the expressions of pro-inflammatory cytokines; suppress the phosphorylation of STAT3 and NF-κB. | (Yuan et al., 2020) |
| Ulcerative colitis | In vivo: DSS-induced ulcerative colitis mouse model. | Down-regulate the expressions of IL-6, TNF-α, IL-1β, MCP-1, CXCL10, COX-2 and Sirt1; inhibit the acetylation of NF-κB; reduce macrophage M1 polarization. | (Liu et al., 2020b) | ||
| Anti-diabetes | Renal tissue | In vitro: AGEs treated podocytes; in vivo: KK-Ay mice. | Decrease FBG, Scr and BUN levels; increase serum insulin level; alleviate podocyte loss and apoptosis; activate RAGE/p38 MAPK/NF-κB and RAGE/NOX4/NF-κB pathways in podocytes. | (Chen et al., 2020) | |
| Liver | In vitro: serum-free DMEM with 50mmol/L glucose treated HepG2 cells; in vivo: DM mice model (single intraperitoneal injection of 60 mg/kg STZ). | Promote glucose uptake; decrease FBG levels in DM mice; down-regulate MDA level and Aldose reductase activity. | (He et al., 2016) | ||
| DM | In vitro: kinetic and molecular docking studies. | Inhibit aldose reductase activity. | (Lee et al., 2015) | ||
| Renal tissue | In vitro: high glucose (30mmol/L) treated HBZY-1 mesangial cells. | Inhibit the expression of FN and IL-6. | (Ma et al., 2014) | ||
| Renal tissue | In vitro: high glucose (27.5mmolL) treated HK-2 cells; in vivo: DM rats model (single intraperitoneal injection of 45 mg/kg STZ). | Inhibit CTGF expression in vitro and in vivo. | (Jiang et al., 2012) | ||
| Liver | In vivo: db/db mice. | Decrease serum glucose and elevate serum leptin; inhibit ROS and lipid peroxidation in the serum and liver; down-regulate the expressions of NOX4 and p22phox; down-regulate the expressions of NF-κB, COX-2, iNOS and MCP-1. | (Park et al., 2011b) | ||
| Hepatic and renal tissue | In vivo: db/db mice. | Decrease serum glucose, TG, LDL/VLDL and increase serum HDL; elevate GSH/GSSG ratio; up-regulate PPARα expression; down-regulate SREBP-1, SREBP-2 expressions; inhibit AGEs formation and RAGE expression in hepatic and renal tissues. | (Yamabe et al., 2010) | ||
| Renal tissue | In vitro: AGEs treated rat mesangial cells. | Inhibit AGEs-induced mesangial cells proliferation and cell cycle; down-regulate ROS and MDA; up-regulate SOD and GSH. | (Xu et al., 2006) | ||
| Anti-cholinesterase | Alzheimer's disease | In vivo: scopolamine (1 mg/kg, s.c.)-induced amnesic mice. | Mitigate scopolamine-induced memory deficits in passive avoidance test and Morris water maze test; inhibit acetylcholinesterase activity in the mouse hippocampus. | (Lee et al., 2009) | |
| Ursolic acid | Anti-diabetes | Liver | In vitro: serum-free DMEM with 50mmol/L glucose treated HepG2 cells; in vivo: DM mice model(single intraperitoneal injection of 60 mg/kg STZ). | Inhibit α-glucosidase activity; promote glucose uptake; decrease FBG level in DM mice; down-regulate MDA and Aldose reductase activity, up-regulate SOD activity. | (He et al., 2016) |
| Anti-inflammation | Colitis | In vitro: LPS-treated peritoneal macrophages; in vivo: TNBS-induced colitis mice. | Inhibit phosphorylation of IRAK1, TAK1, IKKβ, and IkappaBalpha; inhibit the activation of NF-κB and MAPKs; inhibit IL-1β, IL-6, TNF-α, COX-2 and iNOS expression as well as PGE2 and NO levels; inhibit LPS bind to TLR4 on immune cells. | (Jang et al., 2014) | |
| Inhibit mucin secretion | Airway diseases | In vitro: EGF (25 ng/mL) or PMA (10 ng/mL) treated NCI-H292 cells (the human pulmonary mucoepidermoid carcinoma cell line). | Inhibit MUC5AC mucin gene expression and mucin protein production. | (Cho et al., 2011) | |
| Antioxidation | Inner ear diseases | In vitro: H2O2-treated HEI-OC1 auditory cells. | Reduce lipid peroxidation; up-regulate the activities of CAT and GPX. | (Yu et al., 2009) | |
| Oleanolic Acid | Anti-proliferation | Benign prostatic hyperplasia | In vitro: Human BPH-1 cells; in vivo: BPH rat model (male rats injected with testosterone propionate). | Decrease prostate weight and prostate epithelial thickness; reduce serum DHT and 5α-reductase mRNA levels; down-regulate protein expressions of bcl-2, bcl-xL and PCNA; down-regulate the cell cycle markers CdK4-cyclin D1 and CdK2-cyclin E. | (Cheon et al., 2020) |
| Inhibit mucin secretion | Airway diseases | In vitro: EGF (25 ng/mL) or PMA (10 ng/mL) treated NCI-H292 cells. | Inhibit MUC5AC mucin gene expression and mucin protein production. | (Cho et al., 2011) | |
| Anti-diabetes | DM | In vivo: intraperitoneal inject into the fasting Wistar rats. | Enhance the release of ACh from nerve terminals, stimulate muscarinic M(3) receptors in the pancreatic β cells and augment the insulin release. | (Hsu et al., 2006) | |
| Cornuside | Anti-cholinesterase | Alzheimer's disease | In vitro experiments. | Inhibit ChEs and BACE1 by interacting with both the catalytic active sites and the peripheral anionic sites. | (Bhakta et al., 2017) |
| Vasorelaxant activity | In vitro: isometric vascular tone of phenylephrine-contracted thoracic aortae; cGMP production in HUVECs. | Dilates vascular smooth muscle via endothelium-dependent NO/cGMP signaling. | (Kang et al., 2007) | ||
| Polymeric proanthocyanidins | Anti-cholinesterase | Alzheimer's disease | In vitro experiments. | Inhibit ChEs and BACE1 by interacting with both the catalytic active sites and the peripheral anionic sites. | (Bhakta et al., 2017) |
| Anti-diabetes | DM | In vivo: male Wistar rats with normal blood glucose. | Inhibit α-glucosidase activity; improve the oral sucrose tolerance, and inhibit the rise in the plasma glucose levels in normal rats. | (Park et al., 2011c) | |
| 1,2,3-tri-O-galloyl-beta-D-glucose | Anti-cholinesterase | Alzheimer's disease | In vitro experiments. | Inhibit ChEs and BACE1 by interacting with both the catalytic active sites and the peripheral anionic sites. | (Bhakta et al., 2017) |
| Anti-diabetes | DM | In vitro experiments. | Inhibit the formation of AGEs and RLAR, inhibit AGE-BSA cross-linking. | Lee et al. (2011) | |
| 1,2,3,6-tetra-O-galloyl-beta-D-glucose | Anti-cholinesterase | Alzheimer's disease | In vitro experiments. | Inhibit ChEs and BACE1 by interacting with both the catalytic active sites and the peripheral anionic sites. | (Bhakta et al., 2017) |
| Anti-diabetes | DM | In vitro experiments. | Inhibit the formation of AGEs and RLAR, inhibit AGE-BSA cross-linking; prevent the opacity of lenses. | (Lee et al., 2011) | |
| 1,2,6-tri-O-galloyl-beta-D-glucose | Anti-diabetes | Diabetes mellitus(DM) | In vitro experiments. | Inhibit the formation of AGEs and RLAR, inhibit AGE-BSA cross-linking; prevent the opacity of lenses. | (Lee et al., 2011) |
| 1,2,4,6-tetra-O-galloyl-bta-D-glucose | Anti-diabetes | Diabetes mellitus(DM) | In vitro experiments. | Inhibit the formation of AGEs and RLAR, inhibit AGE-BSA cross-linking; prevent the opacity of lenses. | (Lee et al., 2011) |
| 1,2,3,4,6-penta-O-galloyl-beta-Dglucose | Anti-diabetes | Diabetes mellitus(DM) | In vitro experiments. | Inhibit the formation of AGEs and RLAR, inhibit AGE-BSA cross-linking; prevent the opacity of lenses. | (Lee et al., 2011) |
| Tellimagrandin I | Anti-cholinesterase | Alzheimer's disease | In vitro experiments. | Inhibit ChEs and BACE1 by interacting with both the catalytic active sites and the peripheral anionic sites. | (Bhakta et al., 2017) |
| Tellimagrandin II | Anti-cholinesterase | Alzheimer's disease | In vitro experiments. | Inhibit ChEs and BACE1 by interacting with both the catalytic active sites and the peripheral anionic sites. | (Bhakta et al., 2017) |
| Anti-diabetes | DM | In vitro experiments. | Inhibit the formation of AGEs and RLAR, inhibit AGE-BSA cross-linking; prevent the opacity of lenses. | (Lee et al., 2011) | |
| Isoterchebinc | Anti-cholinesterase | Alzheimer's disease | In vitro experiments. | inhibit ChEs and BACE1 by interacting with both the catalytic active sites and the peripheral anionic sites. | (Bhakta et al., 2017) |
| 7-O-Galloyl-D-sedoheptulose | Anti-diabetes | Hepatic tissue | In vivo: db/db mice. | Decrease serum glucose, leptin, insulin, TNF-α, IL-6, resistin, ALT, AST; reduce hepatic AGEs, RAGE and ROS; reduce hepatic p-ERK1/2, p-cJNK, NF-κB, AP-1, MCP-1, ICAM-1, TNF-α, and IL-6. | (Park et al., 2015b) |
| DM | In vitro: kinetic and molecular docking studies. | inhibit aldose reductase activity | (Lee et al., 2015) | ||
| Adipose tissue | In vivo: db/db mice. | Decrease serum glucose, leptin, insulin, C-peptide, resistin, TNF-α, IL-6, TG, TC, HDL, VLDL/LDL, ROS and TBARS; up-regulate serum adiponectin; decrease adipose tissue lipid, ROS, TBARS contents and SREBP-1, NF-κB, COX-2, iNOS, MCP-1, ICAM-1, p-cJNK, AP-1, TGF-β1, bax, cytochrome c , caspase-3 expressions; elevate PPARα, PPARγ, and β-cell lymphoma 2 in the adipose tissue. | (Park et al., 2013) | ||
| Renal tissue | In vivo: db/db mice. | Decrease serum insulin, Cr and BUN levels; down-regulate serum TNF-α, IL-6 and ROS; down-regulate renal ROS, TBARS, NF-κBp65, NOX4, p22phox, COX-2, iNOS, bax and Cytochrome C; up-regulate GSH/GSSG ratio. | (Park et al., 2012) | ||
| Hepatic and renal tissue | In vivo: db/db mice. | Down-regulated the expression of SREBP-1; inhibit AGEs formation and RAGE expression in hepatic and renal tissues. | (Park et al., 2010a) | ||
| Malic acid | Anti-platelet | In vitro: platelet viability assay and platelet adhesion assay. | Inhibit platelet aggregation and prevent platelet adhesion. | (Zhang et al., 2013) | |
| Succinic acid | Anti-platelet | In vitro: platelet viability assay and platelet adhesion assay. | Inhibit platelet aggregation and prevent platelet adhesion. | (Zhang et al., 2013) | |
| Citric acid | Anti-platelet | In vitro: platelet viability assay and platelet adhesion assay. | Inhibit platelet aggregation and prevent platelet adhesion. | (Zhang et al., 2013) | |
| 7-O-butylmorroniside | Neuroprotection | Neurodegenerative diseases | In vitro: glutamate-treated HT22 hippocampal cells. | Elevate the cell viability (MTT) of glutamate-treated HT22 hippocampal cells. | (Jeong et al., 2012) |
| 5-hydroxymethylfurfuralc (processed C. officinalis) | Anti-diabetes | Vascular system | In vitro: high glucos treated HUVECs. | Inhibit HUVECs apoptosis induced by high glucose; reduce ROS and superoxide; down-regulate the expressions of IL-8, JNK1 and JNK2/3; up-regulated the expression of p-Akt. | (Cao et al., 2013) |
| Antioxidation | Acute liver injury | In vitro: H2O2-treated human vein epidermal cell ; in vivo: CCL4-induced acute liver injury mice. | Protect human vein epidermal cell against H2O2; decrease ALT, AST in acute liver injury in mice. | (Ding et al., 2008) |
Notes: Abbreviations of table 1.
NLRP3: NOD-like receptors three; MMP: matrix metalloprotein; STAT: signal transducer and activator of transcription; GLP: glucagon-like peptide-1; BMSCs: bone marrow mesenchymal stem cells; Glo1: glyoxalase-1; FBG: fasting blood glucose; SREBP: sterol-regulatory element binding proteins; GSSG: oxidized glutathione; HFD: high-fat diet; SR-A1: type A1 scavenger receptor; LPS: lipopolysaccharide; DSS: dextran sodium sulfate; TNF-α: tumor necrosis factor-α; CXCL10: CXC chemokine ligand-10; CTGF: connective tissue growth factor; TNBS: 2,4,6-trinitrobenzenesulfonic acid; IRAK: interleukin one receptor-associated kinase; IKKβ: inhibitor of nuclear factor kappaB kinase subunit β; PGE2: prostaglandin E2; TLR4: toll-like receptor four; EGF: epidermal growth factor; PMA: phorbol 12-myristate 13-acetate; GPX: glutathione peroxidase; DHT: dihydrotestosterone; PCNA: proliferating cell nuclear antigen; HUVECs: human umbilical vein endothelial cells; RLAR: rat lens aldose reductase; AP-1: activator protein-1; TBARS: thiobarbituric acid-reactive substance.