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Fulltext Vasorelaxant effect of diterpenoid lactones from Andrographis paniculata chloroform extract on rat aortic rings

Sriramaneni RN, Omar AZ, Ibrahim SM, Amirin S, Mohd Zaini A

Pharmacognosy Res, 2010 Jul;2(4):242-6.
PMID: 21808575 DOI: 10.4103/0974-8490.69125

BACKGROUND: The aim of the present study is to evaluate the possible mechanism of the vasorelaxant effect of the Andrographis paniculata chloroform extract (APCE) and diterpenoids, such as, 14-deoxyandrographolide (DA) and 14-deoxy-11, 12-didehydroandrographolide (DDA), on rat aortic rings.
METHODS: DA and DDA (10 μM to 40 μM) induce relaxation in the aortic rings pre-contracted with KCl (80 mM).
RESULTS: The IC(50) values are 40.47 ± 1.44 and 37.43 ± 1.41%, respectively, and this inhibition is antagonized by increasing the Ca(2+) concentration in the Kreb's medium. The results indicate that APCE, DA, and DDA may have a calcium anatgonist property. APCE, DA, and DDA also relax norepinephrene (NE)-induced sustained contractions with IC(50) values 41.63 ± 1.19, 49.22 ± 2.76, and 37.46 ± 1.41% and this relaxant effect is unaffected by the removal of the endothelium or by the presence of indomethacin and Nω-nitro-L-arginine (L-NAME). Moreover, DA and DDA inhibit the phasic and tonic contractions induced by NE in a concentration-dependent manner and show the most potent inhibition on phasic contraction (P < 0.01).
CONCLUSION: This study shows that APCE, DA, and DDA pre-treatment presents a more potent inhibition compared to post-treatment, after the tension has reached a steady state. These results suggest that the vasorelaxation of APCE, DA, and DDA direct the inhibition of the calcium influx. The vasorelaxant effect is more active in the calcium independent pathway and more sensitive in the intial stage of contraction.
Current updates on pharmacological roles of glucagon-like peptide 1 in obesity

Verma RK, Sriramaneni R, Pandey M, Chaudhury H, Gorain B, Gupta G

Panminerva Med, 2018 Dec;60(4):224-225.
PMID: 29856185 DOI: 10.23736/S0031-0808.18.03479-1
Cardiovascular activity of the n-butanol fraction of the methanol extract of Loranthus ferrugineus Roxb

Ameer OZ, Salman IM, Siddiqui MJ, Yam MF, Sriramaneni RN, Sadikun A, et al.

Braz. J. Med. Biol. Res., 2010 Feb;43(2):186-94.
PMID: 20084331

We investigated the vascular responses and the blood pressure reducing effects of different fractions obtained from the methanol extract of Loranthus ferrugineus Roxb. (F. Loranthaceae). By means of solvent-solvent extraction, L. ferrugineus methanol extract (LFME) was successively fractionated with chloroform, ethyl acetate and n-butanol. The ability of these LFME fractions to relax vascular smooth muscle against phenylephrine (PE)- and KCl-induced contractions in isolated rat aortic rings was determined. In another set of experiments, LFME fractions were tested for blood pressure lowering activity in anesthetized adult male Sprague-Dawley rats (250-300 g, 14-18 weeks). The n-butanol fraction of LFME (NBF-LFME) produced a significant concentration-dependent inhibition of PE- and KCl-induced aortic ring contractions compared to other fractions. Moreover, NBF-LFME had a significantly higher relaxant effect against PE- than against high K+-induced contractions. In anesthetized Sprague-Dawley rats, NBF-LFME significantly lowered blood pressure in a dose-dependent manner and with a relatively longer duration of action compared to the other fractions. HPLC, UV and IR spectra suggested the presence of terpenoid constituents in both LFME and NBF-LFME. Accordingly, we conclude that NBF-LFME is the most potent fraction producing a concentration-dependent relaxation in vascular smooth muscle in vitro and a dose-dependent blood pressure lowering activity in vivo. The cardiovascular effects of NBF-LFME are most likely attributable to its terpenoid content.
Nrf2/HO-1 Mediated Protective Activity of Genistein Against Doxorubicin-Induced Cardiac Toxicity

Chen M, Samuel VP, Wu Y, Dang M, Lin Y, Sriramaneni R, et al.

J Environ Pathol Toxicol Oncol, 2019;38(2):143-152.
PMID: 31679277 DOI: 10.1615/JEnvironPatholToxicolOncol.2019029341

The current study evaluated the cardioprotective activity of genistein in cases of doxorubicin-(Dox) induced cardiac toxicity and a probable mechanism underlying this protection, such as an antioxidant pathway in cardiac tissues. Animals used in this study were categorized into four groups. The first group was treated with sodium carboxymethylcellulose (0.3%; CMC-Na) solution. The second group received Dox (3.0 mg/kg, i.p.) on days 6, 12, 18, and 24. The third and fourth groups received Dox (3 mg/kg, i.p.) on days 6, 12, 18, and 24 and received protective doses of genistein (100 [group 3] and 200 [group 4] mg/kg/day, p.o.) for 30 days. Treatment with genistein significantly improved the altered cardiac function markers and oxidative stress markers. This was coupled with significant improvement in cardiac histopathological features. Genistein enhanced the Nrf2 and HO-1 expression, which showed protection against oxidative insult induced by Dox. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed substantial inhibition of apoptosis by genistein in myocardia. The study showed that genistein has a strong reactive oxygen species scavenging property and potentially (P ≤ .001) decreases the lipid peroxidation as well as inhibits DNA damage in cardiac toxicity induced by Dox. In conclusion, the potential antioxidant effect of genistein may be because of its modulatory effect on Nrf2/HO-1 signalling pathway and by this means exhibits cardioprotective effects from Dox-induced oxidative injury.