Swertiamarin

Effects of gentiopicroside, sweroside and swertiamarine, secoiridoids from gentian (Gentiana lutea ssp. symphyandra), on cultured chicken embryonic fibroblasts.[Pubmed: 16557467]

Planta Med. 2006 Mar;72(4):289-94.

Wound healing properties of Gentian (Gentiana lutea ssp. symphyandra) extract and its main constituents, gentiopicroside, sweroside and Swertiamarine (compounds 1-3, respectively) were evaluated by comparison with dexpanthenol on cultured chicken embryonic fibroblasts.
METHODS AND RESULTS:
The extract was also analyzed by HPLC to quantify its constituents. Chicken embryonic fibroblasts from fertilized eggs were incubated with the plant extract and its constituents, compounds 1-3. Using microscopy, mitotic ability, morphological changes and collagen production in the cultured fibroblasts were evaluated as parameters. Wound healing activity of Gentian seems to be mainly due to the increase in the stimulation of collagen production and the mitotic activity by compounds 2 and 3, respectively (p < 0.005 in all cases). All three compounds also exhibited cytoprotective effects, which may cause a synergism in terms of wound healing activity of Gentian.
CONCLUSIONS:
The findings demonstrated the wound healing activity of Gentian, which has previously been based only on ethnomedical data.

Anti-diabetic activity of swertiamarin is due to an active metabolite, gentianine, that upregulates PPAR-γ gene expression in 3T3-L1 cells.[Pubmed: 22718571 ]

Phytother Res. 2013 Apr;27(4):624-7.

We have previously shown the anti-diabetic effects of Swertiamarin; however, pharmacokinetic analysis showed that Swertiamarin had a plasma half-life of 1.3 h. Gentianine is an active metabolite of Swertiamarin that possesses a pharmacophoric moiety. The aim of this study was to explore the possibility whether the anti-diabetic effect of Swertiamarin is due to gentianine.
METHODS AND RESULTS:
Swertiamarin treatment had no significant effect on adipogenesis, or the mRNA expression of PPAR-γ and GLUT-4; however, there was a significant increase in the mRNA expression of adiponectin. On the other hand, treatment with gentianine significantly increased adipogenesis, which was associated with a significant increase in the mRNA expression of PPAR-γ, GLUT-4 and adiponectin.
CONCLUSIONS:
These findings suggest, for the first time, that the anti-diabetic effect of Swertiamarin is due to gentianine, an active metabolite of Swertiamarin.

Antioxidant and hepatoprotective effect of swertiamarin from Enicostemma axillare against D-galactosamine induced acute liver damage in rats.[Pubmed: 20420896 ]

J Ethnopharmacol. 2010 Jul 6;130(1):103-6.

The whole plant of Enicostemma axillare Raynal (Family: Gentianaceae) is used in variety of diseases in traditional Indian system of medicine including hepatic ailments. Swertiamarin isolated from Enicostemma axillare Raynal was evaluated for antioxidant and hepatoprotective activity.
METHODS AND RESULTS:
Swertiamarin was isolated from successive ethyl acetate extract of the plant Enicostemma axillare belongs to the family Gentianaceae. The concentration of Swertiamarin was determined by high performance thin layer chromatography (HPTLC). The hepatoprotective and antioxidant activity of Swertiamarin (100 and 200mg/kg body weight) was carried out against d-Galactosamine (d-GalN) (200mg/kg body weight intraperitoneally i.p.) induced liver injury in rats. Swertiamarin a secoiridoid glycoside was found to contain a major constituent of the extract. d-GalN caused significant hepatotoxicity by alteration of several hepatic parameters. It also caused significant lipid peroxidation and reduced the levels of antioxidant defense mechanisms. The treatment with Swertiamarin at 100 and 200mg/kg body weight when administered orally for 8 days prior to d-GalN caused a significant restoration of all the altered biochemical parameters due to d-GalN towards the normal, indicating the potent antioxidant and hepatoprotective nature of Swertiamarin.
CONCLUSIONS:
Swertiamarin isolated from Enicostemma axillare possesses significant antioxidant and hepatoprotective properties against d-GalN induced hepatotoxicity given at 100 and 200mg/kg body weight orally for 8 days, which might be due to its in vitro antioxidant activity.

Antihyperlipidaemic activity of swertiamarin, a secoiridoid glycoside in poloxamer-407-induced hyperlipidaemic rats.[Pubmed: 19633811]

J Nat Med. 2009 Oct;63(4):437-42.

METHODS AND RESULTS:
We have investigated antihyperlipidaemic effect of Swertiamarin (50 mg/kg, oral once) isolated from the perennial herb Enicostemma littorale Blume in poloxamer 407 (P-407)-induced hyperlipidaemic rats. Rats were made hyperlipidaemic by intraperitoneal administration of P-407 (400 mg/kg). Serum lipid levels such as total cholesterol, triglycerides and low-density lipoprotein cholesterol increased significantly (P < 0.001) compared with normal control rats. All these changes were significantly prevented in the rats treated with Swertiamarin. Serum high-density lipoprotein (HDL) cholesterol was found to be reduced in the P-407 control rats. However, administration of Swertiamarin significantly (P < 0.01) increased HDL levels and it showed a significant lipid-lowering effect, as well as a high antiatherogenic potential.
CONCLUSIONS:
Overall Swertiamarin is an effective lipid-lowering lead compound and can be useful for preventing atherosclerosis.

Effects of Swertia japonica extract and its main compound swertiamarin on gastric emptying and gastrointestinal motility in mice.[Pubmed: 21571047 ]

Fitoterapia. 2011 Sep;82(6):827-33.

The Swertia japonica is used clinically as a remedy for gastrointestinal symptoms in Japan.
METHODS AND RESULTS:
We examined the effects of a S. japonica and Swertiamarin on gastric emptying and gastrointestinal motility in atropine-, dopamine-, and 5-hydroxytryptamine (5-HT)-treated mice. All three preparations inhibited reductions in gastric emptying and gastrointestinal motility induced by dopamine (1mg/kg, intraperitoneal injection, ip). Neither the powder, Swertiamarin, nor itopride had any effect on the reductions in gastric emptying and gastrointestinal motility caused by 5-HT (4 mg/kg, ip).
CONCLUSIONS:
These findings suggest that the powder and Swertiamarin stimulate gastric emptying and gastrointestinal motility by inhibiting the dopamine D(2) receptor.

Swertiamarin attenuates inflammation mediators via modulating NF-κB/I κB and JAK2/STAT3 transcription factors in adjuvant induced arthritis.[Pubmed: 24582615]

Role of 5-HT2 receptors in diabetes: Swertiamarin seco-iridoid glycoside might be a possible 5-HT2 receptor modulator.[Pubmed: 25708274]

Physiol Behav. 2015 May 15;144:66-72.

In the present review, we are focusing on modulators of 5-HT2 receptors, Swertiamarin and their role in diabetes. These drugs possess both central and peripheral actions in various animal models of depression, diabetes and obesity.
METHODS AND RESULTS:
Swertiamarin and 5-HT2 antagonist are reported antidepressant, hypolipidemic and beneficial in peripheral vasculopathy. In contrast to this, 5-HT2C selective agonist decreases hyperglycemia, hyperlipidemia and insulin secretogogue by action. Selective serotonin reuptake inhibitors (SSRIs) are known antidepressant having weight gain as an adverse effect. Swertiamarin has similar pharmacological actions as 5-HT2 antagonist and 5-HT2C selective agonist. This warrants that Swertiamarin might modulate 5-HT2 receptors rather than affecting the uptake of serotonin.
CONCLUSIONS:
In the light of present investigation, the mechanism of these drugs can correlate the role of central and peripheral 5-HT2 receptors in diabetes.

Eur J Pharm Sci. 2014 Jun 2;56:70-86.

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease that leads to pannus formation followed by severe joint destruction, characterized by synovial hyperplasia, inflammation and angiogenesis. Swertiamarin is a secoiridoid glycoside that is used as an anti-inflammatory compound, mainly found in Enicostema axillare (Lam) A. Raynal, a medicinal plant used in Indian system of traditional medicine.
METHODS AND RESULTS:
In the present study, the effect of Swertiamarin was evlauated in experimental adjuvant arthritis animal model by the estimation of biochemical (paw thickness, lysosomal enzymes, and urinary degradative products) parameters, proinflammatory cytokines and enzymes along with histopathological and radiographic observations. The proteins of phosphorylated NF-κB/IκB and JAK2/STAT3 transcription factors were also quantified from experimental animals as well as LPS induced RAW 264.7 macrophage cells. In in silico analysis, Swertiamarin was docked with proinflammatory enzymes to confirm its potential. The administration of Swertiamarin (2, 5, 10mg/kg bw) significantly (P⩽0.05) inhibited the levels of paw thickness, lysosomal enzymes and increased the body weight of experimental animals in a dose dependent manner. In molecular analysis, the treatment decreased the release of proinflammatory cytokines (IL1, TNF, IL-6) and proangiogenic enzymes (MMPs, iNOS, PGE2, PPARγ and COX-2); and also significantly (P⩽0.05) increased the levels of antiinflammatory proteins (IL-10, IL-4) when compared to the disease groups. The Swertiamarin treatment significantly (P⩽0.05) inhibited the release of NF-κB p65, p-IκBα, p-JAK2 and p-STAT3 signaling proteins levels on both experimental animals and LPS induced cells. Histopathological and radiological analysis evidenced the curative effect of Swertiamarin on bone destruction. The docking studies of Swertiamarin on proinflammatory enzymes supported the results from the in vivo experiments.
CONCLUSIONS:
Thus the Swertiamarin inhibited the development of arthritis by modulating NF-κB/IκB and JAK2/STAT3 signaling. These findings suggested that Swertiamarin acted as an anti-rheumatic agent.

Antinociceptive activity of swertiamarin isolated from Enicostemma axillare.[Pubmed: 19019644 ]

Immunohistochemistry, histopathology, and biomarker studies of swertiamarin, a secoiridoid glycoside, prevents and protects streptozotocin-induced β-cell damage in Wistar rat pancreas.[Pubmed: 25770453]

J Endocrinol Invest. 2015 Jun;38(6):669-84.

Diabetes mellitus is globally the major cause for metabolic syndrome in STZ-induced diabetic rats, leading to mortality. Treatment of diabetes by oral hypoglycemic agents causes adverse side effects and thus treatment with natural herbal drugs like Swertiamarin is promising. Swertiamarin, an active compound isolated from Enicostemma littorale possesses antidiabetic activity and enhances β cell regeneration which causes reversal of diabetes. The present study aims at the following: (1) to evaluate antidiabetic, anti-hyperlipidaemic, activity of Swertiamarin in Streptozotocin- induced diabetic rats using biomarkers. (2) To assess histopathological alterations in Pancreas, Liver, Kidney, and Heart of Swertiamarin-treated STZ-induced diabetic rats and confirm cytoprotective activity of Swertiamarin by Immunohistochemistry and morphometric investigations.
METHODS AND RESULTS:
Diabetes was induced intraperitoneally in male Wistar rats by Streptozotocin (STZ 50 mg/kg). After STZ-induction, hyperglycemic rats were treated with doses of Swertiamarin orally (15, 25, 50 mg/kg) each for 28 days. Glibenclamide (2.5 mg/kg), a sulphonyl urea, was used as a standard drug. The glycemic control was measured by the biochemical parameter assays. Histopathology analysis of organs and immunohistochemistry of islets were carried out. Our study results showed that oral administration of Swertiamarin at a dosage of 15, 25, 50 mg/kg bw for 28 days resulted in a significant (p < 0.01) decrease in fasting blood glucose, HbA1c, TC, TG, LDL, and increased the levels of hemoglobin, plasma insulin, TP, body weight, and HDL levels significantly (p < 0.01) when compared to STZ-induced diabetic rats, as confirmed by immunohistochemical studies. The effect of Swertiamarin on Carbohydrate-metabolizing enzymes was investigated and found to have normal therapeutic activity. Histopathological studies of Pancreas of Swertiamarin-treated diabetic rats showed regeneration of islets when compared to STZ-induced diabetic rats, as confirmed by immunohistochemical studies.
CONCLUSIONS:
Our research results clearly substantiate that Swertiamarin possesses antihyperglycemic, antihyperlipidemic, cytoprotective, and immune reactivity and also a broad spectrum potential of treating diabetes and other complications related to diabetes and hence can be developed into a potent oral antidiabetic drug.

Phytomedicine. 2009 Mar;16(2-3):227-32.

Many traditional Indian medicinal plants which contain large quantity of a secoiridoid, Swertiamarin are being used to relieve pain. Iridoids present in a wide variety of medicinal plants possess a large number of medicinal properties.
METHODS AND RESULTS:
In the present study in vivo antinociceptive activity of Swertiamarin isolated from E. axillare was carried out using three different methods in mice. In the hot plate method, a significant increase in the latency period was observed for the treatment with Swertiamarin at 100 and 200 mg/kg bw after 30 and 45 min. The percent protection observed after 45 min was 109.42, 147.42 and 157.14, respectively, for the standard paracetamol and Swertiamarin at 100 and 200 mg/kg bw treatments. A significant increase in the tail withdrawal reflex was observed for the Swertiamarin treatment at both the doses with percent protections of 150 and 200, respectively. In both these methods, Swertiamarin produced potent activity than that of standard paracetamol. In the acetic acid induced writhing, Swertiamarin at 100 and 200 mg/kg bw reduced the number of writhes significantly. Dose dependent results were observed in all the three methods and among the two doses, Swertiamarin at 200 mg/kg bw showed potent activity.
CONCLUSIONS:
These results prove that Swertiamarin possess both peripheral and central antinociceptive activity.