Chikusetsusaponin IVa

1 Achyranthes sp. 2 Chenopodium sp. 3 Gardenia sp. 4 Hemsleya sp. 5 Ilex sp. 6 Panax sp. 7 Phytolacca sp.

Chikusetsusaponin IVa a major active ingredient of triterpenoid saponins, exerts antithrombotic effects, including minor hemorrhagic events. This appears to be important for the development of new therapeutic agents. a novel AMPK activator that is capable of bypassing defective insulin signalling and could be useful for the treatment of T2DM or other metabolic disorders. IC50 Value: 199.4 ± 9.1 μM (inhibiting thrombin-induced fibrinogen clotting) Target: In vitro: Using biochemical and pharmacological methods, it proves that chikusetsusaponin IVa prolongs the recalcification time, prothrombin time, activated partial thromboplastin time, and thrombin time of normal human plasma in a dose-dependent manner; inhibits the amidolytic activity of thrombin and factor Xa upon synthetic substrates S2238 and S2222; inhibits thrombin-induced fibrinogen clotting (50% inhibition concentration, 199.4 ± 9.1 μM); inhibits thrombin- and collagen-induced platelet aggregation. Chikusetsusaponin IVa can also preferentially inhibits thrombin in a competitive manner (K(i)=219.6 μM) [1]. Chikusetsusaponin IVa suppresses the production of iNOS, COX-2, IL-1β, IL-6, and TNF-α in LPS-stimulated THP-1 cells likely by inhibiting NF-κB activation and ERK, JNK, and p38 signal pathway phosphorylation [2]. In vivo: Studies were performed on type 2 diabetic mellitus (T2DM) rats given CHS for 28 days to test the antihyperglycemic activity. Oral administration of CHS dose-dependently increased the level of serum insulin and decreased the rise in blood glucose level [3].

References:
[1]. Wang H, et al.Inhibitory effects of Chikusetsusaponin IVa on lipopolysaccharide-induced pro-inflammatory responses in THP-1 cells. Int J Immunopathol Pharmacol. 2015 Jul 8. [2]. Cui J, et al. Insulinotropic effect of Chikusetsu saponin IVa in diabetic rats and pancreatic β-cells. J Ethnopharmacol. 2015 Apr 22;164:334-9. [3]. Li Y, et al. Chikusetsu saponin IVa regulates glucose uptake and fatty acid oxidation: implications in antihyperglycemic and hypolipidemic effects. J Pharm Pharmacol. 2015 Jul;67(7):997-1007. [4]. Dahmer T, et al. Antithrombotic effect of chikusetsusaponin IVa isolated from Ilex paraguariensis (Maté). J Med Food. 2012 Dec;15(12):1073-80.

Insulinotropic effect of Chikusetsu saponin IVa in diabetic rats and pancreatic beta-cells.[Pubmed:25701750]

J Ethnopharmacol. 2015 Apr 22;164:334-9.

ETHNOPHARMACOLOGICAL RELEVANCE: As a well-known traditional Chinese medicine the root bark of Aralia taibaiensis has traditionally been used as the medicine considered alleviating several disorders including diabetes mellitus (DM). Chikusetsu saponin IVa (CHS) has been defined as a major active ingredient of triterpenoid saponins extracted from Aralia taibaiensis. The scientific evidence of anti-diabetic effect for CHS remains unknown and the purpose of our study was to study its hypoglycemic and insulin secretagogue activities. MATERIALS AND METHODS: In vivo studies were performed on type 2 diabetic mellitus (T2DM) rats given CHS for 28 days to test the antihyperglycemic activity. The in vitro effects and possible mechanisms of CHS on the insulin secretion in pancreatic beta-cell line betaTC3 were determined. RESULTS: Oral administration of CHS dose-dependently increased the level of serum insulin and decreased the rise in blood glucose level in an in vivo treatment. In vitro, CHS potently stimulated the release of insulin from betaTC3 cells at both basal and stimulatory glucose concentrations, the effect which was changed by the removal of extracellular Ca(2+). Two methods showed that CHS enhanced the intracellular calcium levels in betaTC3 cells. CHS was capable of enhancing the phosphorylation of extracellular signal-regulated protein kinases C (PKC), which could be reversed by a PKC inhibitor (RO320432), and the insulin secretion induced by CHS was also inhibited by RO320432. Further study also showed that the insulinotropic effect, intracellular calcium levels and the phosphorylation of PKC were reduced by inhibiting G protein-coupled receptor 40 (GPR40) by a GPR40 inhibitor (DC126026). CONCLUSION: These observations suggest that the signaling of CHS-induced insulin secretion from betaTC3 cells via GPR40 mediated calcium and PKC pathways and thus CHS might be developed into a new potential for therapeutic agent used in T2DM patients.

Antithrombotic effect of chikusetsusaponin IVa isolated from Ilex paraguariensis (Mate).[Pubmed:23134458]

J Med Food. 2012 Dec;15(12):1073-80.

The triterpene Chikusetsusaponin IVa was isolated from the fruit of Ilex paraguariensis. Using biochemical and pharmacological methods, we demonstrated that Chikusetsusaponin IVa (1) prolongs the recalcification time, prothrombin time, activated partial thromboplastin time, and thrombin time of normal human plasma in a dose-dependent manner, (2) inhibits the amidolytic activity of thrombin and factor Xa upon synthetic substrates S2238 and S2222, (3) inhibits thrombin-induced fibrinogen clotting (50% inhibition concentration, 199.4 +/- 9.1 muM), and (4) inhibits thrombin- and collagen-induced platelet aggregation. The results also indicate that Chikusetsusaponin IVa preferentially inhibits thrombin in a competitive manner (K(i)=219.6 muM). Furthermore, when administered intravenously to rats, Chikusetsusaponin IVa inhibited thrombus formation in a stasis model of venous thrombosis, although it did not induce a significant bleeding effect. Chikusetsusaponin IVa also prolonged the ex vivo activated partial thromboplastin time. Altogether, these data suggest that Chikusetsusaponin IVa exerts antithrombotic effects, including minor hemorrhagic events. This appears to be important for the development of new therapeutic agents.

Chikusetsu saponin IVa regulates glucose uptake and fatty acid oxidation: implications in antihyperglycemic and hypolipidemic effects.[Pubmed:25677570]

J Pharm Pharmacol. 2015 Jul;67(7):997-1007.

OBJECTIVES: The aim of this study is to investigate antidiabetic effects and molecular mechanisms of the chemical Chikusetsu saponin IVa (CHS) that isolated from root bark of Aralia taibaiensis, which has multiple pharmacological activity, such as relieving rheumatism, promoting blood circulation to arrest pain and antidiabetic action. METHODS: Rats with streptozotocin/nicotinamide-induced type 2 diabetes mellitus (T2DM) and insulin-resistant myocytes were used. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) and acetyl-CoA carboxylase were quantified by immunoblotting. Assays of glucose uptake, fatty acid oxidation, glucose transporter 4 (GLUT4) translocation and carnitine palmitoyl transferase-1 (CPT-1) activity were performed. KEY FINDINGS: Chronic oral administration of CHS effectively decreases blood glucose, triglyceride, free fatty acid (FFA) and low density lipoprotein-cholesterol levels in T2DM rats. In both normal and insulin-resistant C2C12 myocytes, CHS activates AMPK, and increases glucose uptake or fatty acid oxidation through enhancing membrane translocation of GLUT4 or CPT-1 activity respectively. Knockdown of AMPK significantly diminishes the effects of CHS on glucose uptake and fatty acid oxidation. CONCLUSIONS: CHS is a novel AMPK activator that is capable of bypassing defective insulin signalling and could be useful for the treatment of T2DM or other metabolic disorders.

Chikusetsusaponin IVa methyl ester induces cell cycle arrest by the inhibition of nuclear translocation of beta-catenin in HCT116 cells.[Pubmed:25749342]

Biochem Biophys Res Commun. 2015 Apr 17;459(4):591-6.

We demonstrate that Chikusetsusaponin IVa methyl ester (CME), a triterpenoid saponin from the root of Achyranthes japonica, has an anticancer activity. We investigate its molecular mechanism in depth in HCT116 cells. CME reduces the amount of beta-catenin in nucleus and inhibits the binding of beta-catenin to specific DNA sequences (TCF binding elements, TBE) in target gene promoters. Thus, CME appears to decrease the expression of cell cycle regulatory proteins such as Cyclin D1, as a representative target for beta-catenin, as well as CDK2 and CDK4. As a result of the decrease of the cell cycle regulatory proteins, CME inhibits cell proliferation by arresting the cell cycle at the G0/G1 phase. Therefore, we suggest that CME as a novel Wnt/beta-catenin inhibitor can be a putative agent for the treatment of colorectal cancers.

Chikusetsusaponin IVa a major active ingredient of triterpenoid saponins, exerts antithrombotic effects, including minor hemorrhagic events.

Chikusetsusaponin IVa,51415-02-2,Calenduloside F,Natural Products, buy Chikusetsusaponin IVa , Chikusetsusaponin IVa supplier , purchase Chikusetsusaponin IVa , Chikusetsusaponin IVa cost , Chikusetsusaponin IVa manufacturer , order Chikusetsusaponin IVa , high purity Chikusetsusaponin IVa