Bacopaside II

Int J Mol Sci. 2018 Feb 26;19(3). pii: E653.

The Aquaporin 1 Inhibitor Bacopaside II Reduces Endothelial Cell Migration and Tubulogenesis and Induces Apoptosis.[Pubmed: 29495367]

Expression of aquaporin-1 (AQP1) in endothelial cells is critical for their migration and angiogenesis in cancer.
METHODS AND RESULTS:
We tested the AQP1 inhibitor, Bacopaside II, derived from medicinal plant Bacopa monnieri, on endothelial cell migration and tube-formation in vitro using mouse endothelial cell lines (2H11 and 3B11) and human umbilical vein endothelial cells (HUVEC). The effect of Bacopaside II on viability, apoptosis, migration and tubulogenesis was assessed by a proliferation assay, annexin-V/propidium iodide flow cytometry, the scratch wound assay and endothelial tube-formation, respectively. Cell viability was reduced significantly for 2H11 at 15 μM (p = 0.037), 3B11 at 12.5 μM (p = 0.017) and HUVEC at 10 μM (p < 0.0001). At 15 μM, the reduced viability was accompanied by an increase in apoptosis of 38%, 50% and 32% for 2H11, 3B11 and HUVEC, respectively. Bacopaside II at ≥10 μM significantly reduced migration of 2H11 (p = 0.0002) and 3B11 (p = 0.034). HUVECs were most sensitive with a significant reduction at ≥7.5 μM (p = 0.037). Tube-formation was reduced with a 15 μM dose for all cell lines and 10 μM for 3B11 (p < 0.0001).
CONCLUSIONS:
These results suggest that Bacopaside II is a potential anti-angiogenic agent.

Heliyon. 2016 Feb 15;2(2):e00068.

Beneficial effects of Bacopa monnieri extract on opioid induced toxicity.[Pubmed: 27441247]

The present study examined the hepatotoxicity and nephrotoxicity of morphine and illicit street heroin and their amelioration by a standardized methanolic extract of Bacopa monnieri (L.) (mBME) in rats.
METHODS AND RESULTS:
Morphine or street heroin was administered at a dose of 20 mg/kg for 14 and 21 days. mBME (40 mg/kg) or ascorbic acid (50 mg/kg) was administered two hours before morphine or street heroin. High performance liquid chromatography (HPLC) was used for the standardization of bacoside-A major components in mBME. The antioxidant potential of mBME was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. Administration of morphine and street heroin resulted in marked elevation of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine. Histopathological changes induced by morphine and street heroin after 14 days were of reversible nature while treatment for 21 days was associated with irreversible changes. Pretreatment with mBME or ascorbic acid restored the elevation of serum ALT, AST and creatinine and protected liver and kidneys from the toxicological influence of morphine and street heroin. HPLC analysis showed that mBME contained bacoside-A major components i.e. bacoside A3 (37.5 μg/mg), Bacopaside II (4.62 μg/mg) and bacopasaponin C (1.91 μg/mg). The EC50 for the DPPH free radical scavenging assay revealed that mBME possessed strong antioxidant potential.
METHODS AND RESULTS:
These results concluded that as compared to morphine, street heroin was associated with severe biochemical and histopathological changes in the liver and kidneys. Bacopa monnieri having strong antioxidant potential may provide a beneficial herbal remedy for the efficient management of opioid related hepatotoxicity and nephrotoxicity.

Xenobiotica. 2015;45(8):741-9.

In vitro effects of standardized extract of Bacopa monniera and its five individual active constituents on human P-glycoprotein activity.[Pubmed: 25869246 ]

1. For centuries Bacopa monniera (BM) has been used as an herbal drug for the treatment of various mental ailments. A chemically standardized alcoholic extract of BM is clinically available over the counter herbal remedy for memory enhancement in children and adults. Consumption of herbal preparations has been reported to alter the function of membrane transporters, especially P-glycoprotein (P-gp), ATP-dependent drug efflux transporter responsible for the development of herb-drug interactions.
METHODS AND RESULTS:
2. In the present study, we evaluated the in vitro effect of BM extract and its five individual active constituents (namely, bacopaside I, Bacopaside II and bacopasaponin C, bacoside A and bacoside A3) on P-gp function using luminescent P-gp ATPase assay and Rh123 transport assay across human MDR1 gene transfected LLC-GA5-COL150 cell line. 3. It was observed that BM extract and its five individual constituents inhibited both basal activity as well as verapamil-stimulated ATPase activity, suggesting their affinity towards P-gp. Further, BM and its five active constituents inhibited the rhodamine 123 (Rh123) transport across LLC-GA5-COL150 cell monolayer with Bacopaside II being the most potent inhibitor of P-gp, which decreased P-gp efflux ratio of Rh123 by fourfold in comparison to control. 4. 
CONCLUSIONS:
Our finding may prove beneficial in predicting the potential herb-drug interactions of BM on concomitant medication with P-gp substrate drugs in clinical settings.

J Nat Prod. 2007 Apr;70(4):652-5.

Triterpene saponins from Bacopa monnieri and their antidepressant effects in two mice models.[Pubmed: 17343408 ]

METHODS AND RESULTS:
Three new triterpene glycosides, bacopasides VI-VIII (1-3), together with three known analogues, bacopaside I (4), Bacopaside II (5), and bacopasaponsin C (6), were isolated from the whole plant of Bacopa monnieri.
CONCLUSIONS:
Compounds 4, 5, and 6 showed antidepressant activity when tested on forced swimming and tail suspension in mice, respectively.