Gentiopicroside

J Ethnopharmacol. 2015 Aug 22;172:100-7.

Gentiopicroside prevents interleukin-1 beta induced inflammation response in rat articular chondrocyte.[Pubmed: 26116164 ]

In traditional Chinese medicine, Gentiana macrophylla Pall have been prescribed for the treatment of pain and inflammatory conditions. In addition, it is a common Tibetan medicinal herb used for the treatment of tonsillitis, urticaria, and rheumatoid arthritis (RA), while the flowers of G. macrophylla Pall have been traditionally treated as an anti-inflammatory agent to clear heat in Mongolian medicine. The secoiridoid glycosides and their derivatives are the primary active components of G. macrophylla and have been demonstrated to be effective as anti-inflammatory agents.
METHODS AND RESULTS:
Solvent extraction and D101 macroporous resin columns were employed to concentratethe Gentiopicroside. Gentiopicroside cytotoxicity was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; the toxicity of Gentiopicroside in chondrocytes was reconfirmed using Hoechst staining. Western blotting, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry were utilized to explore the protective effects and mechanisms of Gentiopicroside prevents interleukin-1 beta induced inflammation response in rat articular chondrocyte. The MTT assay demonstrated that 50, 500, and 1,500 μg/mL of Gentiopicroside exhibited no significant toxicity to chondrocytes (P>0.05) after 24h. Using immunohistochemistry, ELISA, RT-PCR, Western blot method to explore the protective effect and mechanism of Gentiopicroside on chondrocytes induced by IL-1β. The results showed some pathways of IL-1β signal transduction were inhibited by Gentiopicroside in rat chondrocytes: p38, ERK and JNK. Meanwhile, Gentiopicroside showed inhibition in the IL-1β-induced release of MMPs while increasing Collagen type II expression.
CONCLUSIONS:
The current study demonstrated that Gentiopicroside exhibited a potent protective effect on IL-1β induced inflammation response in rat articular chondrocyte. Thus, Gentiopicroside could be a potential therapeutic strategy for treatment of OA.

Fitoterapia. 2003 Feb;74(1-2):151-4.

Bioactivity of gentiopicroside from the aerial parts of Centaurium erythraea.[Pubmed: 12628413]

Gentiopicroside (1), a secoiridoid glycoside isolated from the methanol extract of the aerial parts of Centaurium erythraea, has been assessed for antibacterial and free radical scavenging activities. General toxicity of 1 has also been determined by brine shrimp lethality bioassay.

Biomed Pharmacother . 2018 Apr;100:142-146.

Gentiopicroside inhibits RANKL-induced osteoclastogenesis by regulating NF-κB and JNK signaling pathways[Pubmed: 29428661]

Gentiopicroside, a main active component from the traditional Chinese herb medicine Gentiana manshurica Kitag, has been shown to possess anti-arthritis effect. However, the molecular mechanism of Gentiopicroside on the osteoclast formation remains unclear. The present study was designed to investigate the effects and mechanisms of Gentiopicroside on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. The results showed that pre-treatment with Gentiopicroside significantly inhibited RANKL-induced osteoclast formation from mouse bone marrow macrophages (BMMs). In addition, we observed that Gentiopicroside efficiently suppressed osteoclastogenesis-related marker genes expression in RANKL-stimulated BMMs. Mechanistically, Gentiopicroside suppressed RANKL-induced the activation of JNK and NF-κB signaling pathways in BMMs. Taken together, the present study demonstrated that Gentiopicroside inhibits RANKL-induced osteoclastogenesis through the inactivation of JNK and NF-κB signaling pathways. Thus, Gentiopicroside may be a promising agent for the treatment of osteoporosis.

Fitoterapia. 2015 Apr;102:127-33.

Effect of gentiopicroside on experimental acute pancreatitis induced by retrograde injection of sodium taurocholate into the biliopancreatic duct in rats.[Pubmed: 25759121]

Gentiopicroside (otherwise known as Gentiopicrin), one of the main active ingredients from the traditional Chinese herb medicine Gentiana manshurica Kitag, presents the effect of attenuating acute pancreatitis in rats.
METHODS AND RESULTS:
The experimental acute pancreatitis was made by retrograde injection of sodium taurocholate into the biliopancreatic duct in rats. Gentiopicroside was given orally and it markedly reduced the pancreatitis-evoked increase of serum amylase and lipase activity, decreased the pancreas mass/body mass index, tissue water content, TNF-α and IL-1β concentrations, and attenuated the histopathological changes and NF-κB p65 protein expression in pancreatic tissue.
CONCLUSIONS:
The results indicate that the function of Gentiopicroside on acute pancreatitis may be related to inhibiting the release of inflammatory mediators and NF-κB p65 protein expression.

Chinese Traditional & Herbal Drugs, 2003, 34(9):814-6

Studies on anti-inflammatory effect of gentiopicroside.[Reference: WebLink]

To study the anti-inflammatory effect of Gentiopicroside extracted from Radix Gentianae Marrophyllae.
METHODS AND RESULTS:
The models of auricular edema in mice induced by dimeth yl benzene, increased permeability of celiac blood capillary and body-twisting reaction induced by acetic acid, paw swelling induced by zymosan A, carrageenan a nd nystatin in rats or in mice were prepared. Then Gentiopicroside was given to the rats or mice by ig. Gentiopicroside inhibited th e auri cular edema, decreased the permeability of celiac blood capillary, reduced the p aw swelling induced by carrageenan and zymosan A, but not by nystation.
CONCLUSIONS:
Gentiopicroside extracted from Radix Gentianae Marrophyllae, exhibits obvious anti-inflammatory effects.

Phytother Res . 2018 Feb;32(2):259-266.

Protective effect of gentiopicroside from Gentiana macrophylla Pall. in ethanol-induced gastric mucosal injury in mice[Pubmed: 29226586]

Gentiopicroside isolated from gentiana macrophylla Pall. belongs to iridoid glycosides. This study aimed to evaluate the protective effect of Gentiopicroside against ethanol-induced gastric mucosal injury in mice. Mice were proactively administrated with Gentiopicroside by intragastric administration once a day for 3 consecutive days. On the 3rd day, gastric ulcer in mice was induced with 70% ethanol after the last intragastric administration. The stomach tissues were submitted for evaluation of the severity of gastric mucosal alterations. Gentiopicroside administrated orally ameliorated the severity of gastric mucosal alterations. Oral administration of Gentiopicroside significantly increased heat shock protein-70 and glutathione levels and superoxide dismutase activity, normalized epidermal growth factor and vascular endothelial growth factor levels, and decreased the levels of tumour necrosis factor-α, interleukin-6 and malondialdehyde, and myeloperoxidase activity in gastric tissue. These findings demonstrated that Gentiopicroside has protective effect against ethanol-induced gastric mucosal injury in mice through the improvements of antioxidative and anti-inflammatory effects, as well as up-regulation of heat shock protein-70 level and normalization of epidermal growth factor and vascular endothelial growth factor levels. The results presented in this study provide some evidence for the development of a novel antigastric ulcer agent.

Drug Metab Pharmacokinet. 2013;28(4):339-44.

In vitro inhibition and induction of human liver cytochrome P450 enzymes by gentiopicroside: potent effect on CYP2A6.[Pubmed: 23419353]

Gentiopicroside (GE), a naturally occurring iridoid glycoside, has been developed into a Novel Traditional Chinese Drug named Gentiopicroside injection, and it was approved for the treatment of acute jaundice and chronic active hepatitis by SFDA. However, the inhibitory and inducible effects of GE on the activity of cytochrome P450 (CYP450) are unclear. The purpose of this study was to evaluate the ability of GE to inhibit and induce human cytochrome P450 enzymes in vitro.
METHODS AND RESULTS:
In human liver microsomes, GE inhibited CYP2A6 and CYP2E1 in a concentration-dependent manner, with IC₅₀ values of 21.8 μg/ml and 594 μg/ml, respectively, and the IC₅₀ of CYP2A6 was close to the C(max) value observed clinically. GE was a non-competitive inhibitor of CYP2A6 at lower concentrations and a competitive inhibitor at higher concentrations. GE did not produce inhibition of CYP2C9, CYP2D6, CYP1A2 or CYP3A4 activities. However, a significant increase of CYP1A2 and CYP3A4 activity was observed at high concentrations. In cultured human hepatocytes no significant induction of CYP1A2, CYP3A4 or CYP2B6 was observed.
CONCLUSIONS:
Given these results, the in vivo potential inhibition of GE on CYP2A6 deserves further investigation, and it seems that the hepatoprotective effect of GE is irrelevant to its effect on P450s.

CNS Neurosci Ther. 2012 Aug;18(8):652-8.

Gentiopicroside attenuates morphine rewarding effect through downregulation of GluN2B receptors in nucleus accumbens.[Pubmed: 22621711]

Gentiopicroside (Gent) is one of the secoiridoid compound isolated from Gentiana lutea. This compound exhibits analgesic activities and inhibits the expression of GluN2B-containing N-methyl-D-aspartate (NMDA) receptors in the anterior cingulate cortex in mice. Nucleus accumbens (NAc) is a forebrain structure known for its role in drug addiction. However, little is known about the role of Gent on morphine dependence and synaptic transmission changes in the NAc.
METHODS AND RESULTS:
Conditioned place preference (CPP) test and behavioral sensitization of locomotor activity were used to investigate drug-seeking related behaviors. Brain slices containing NAc were prepared, and whole-cell patch-clamp recordings were performed to record the excitatory postsynaptic currents (EPSCs). Expression of proteins was detected by Western blot analysis. Systemic administration of Gent attenuated the CPP effect induced by morphine, but had no effect on morphine-induced behavioral sensitization. Gent significantly reversed overexpression of GluN2B-containing NMDA receptors and dopamine D2 receptors in NAc during the first week of morphine withdrawal. However, the compound did not affect the overexpression of GluN2A-containing NMDA receptors, GluA1, and dopamine D1 receptors. Lastly, Gent significantly reduced NMDA receptors-mediated EPSCs in the NAc.
CONCLUSIONS:
Our study provides strong evidence that Gent inhibits morphine dependence through downregulation of GluN2B-containing NMDA receptors in the NAc.

Planta Med. 2000 Dec;66(8):765-7.

Smooth muscle relaxing activity of gentiopicroside isolated from Gentiana spathacea.[Pubmed: 11199140 ]

METHODS AND RESULTS:
Bioassay directed fractionation of the (1:1) chloroform-methanol extract of Gentiana spathacea H.B.K (Gentianaceae) led to the isolation of Gentiopicroside (gentiopricrin) (1), the major spasmolytic component of the plant. Gentiopicroside inhibited, in a concentration-dependent manner, the spontaneous contractions of isolated guinea pig ileum.
CONCLUSIONS:
Contractions induced by histamine, acetylcholine, BaCl2 and KCl on the ileum were also significantly blocked by this monoterpene glucoside, which suggests that this compound might be interfering with calcium influx into the smooth muscle cells.

Int Immunopharmacol. 2016 Oct;39:16-22.

Protective effect of gentiopicroside against dextran sodium sulfate induced colitis in mice.[Pubmed: 27394986 ]

This study was designed to investigate the anti-inflammatory activity of the pure compound Gentiopicroside (Gent) on dextran sulfate sodium (DSS)-induced colitis in a mouse model and to explore the possible related mechanisms.
METHODS AND RESULTS:
Experimental colitis was induced in ICR mice by dissolving 5% DSS in their drinking water for 7days. Gent (200, 100, and 50mg/kg) and 5-aminosalicylic acid (5-ASA, 100mg/kg) were oral administrated once a day for 7days. Anti-inflammatory effects were evaluated by comparing extend of colonic mucosal injury assessed by disease activity index (DAI), colon length, histopathological examination, and biochemical test. The possible mechanisms of Gent activities were explored by evaluating expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 using real-time fluorogenic PCR and expression levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) using Western blotting. The results showed that oral administration of Gent significantly attenuated DSS-induced loss of body weight, diarrhea, shortening of colon length and histological changes, associated with the decrease in the activity of myeloperoxidase (MPO) in the colon. In addition, the mRNA expression of TNF-α, IL-1β, IL-6 and the overexpression of COX-2 and iNOS proteins in the colon were down-regulated by Gent treatment.
CONCLUSIONS:
To our knowledge, this is the first study to demonstrate that Gent treatment can exert anti-inflammatory effects on experimental acute colitis through attenuating the expression levels of TNF-α, IL-1β, IL-6, iNOS and COX-2, and it may present the therapeutic potential in the treatment of colitis.