Synthesis and anti-hyperlipidemic activity of 3H-benzo [4, 5] thieno [2, 3-d] [1, 2, 3] triazin-4-ones: possible mechanism of altered lipid metabolism

The present study was aimed to evaluate the anti-hyperlipidemic activity of newly synthesized tricyclic benzothieno 1, 2, 3-triazine derivatives namely CP-1 [3-[methyl]-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one], CP-2 [3-[ethyl]- 5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one] and CP-6 [3-[2-chloro phenyl]-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one] against dexamethasone and Triton WR-1339-induced hyper- lipidemia in rats. Anti-hyperlipidemic activity of the test compounds were evaluated against dexamethasone [10 mg/kg, subcutaneous [s.c.]] and Triton WR-1339 [200 mg/kg, intraperitoneal [i.p]] induced hyperlipidemia in rats. Administration of single dose of Triton WR-1339 [200 mg/kg i.p] and dexamethasone [10 mg/kg s.c.] for 8 consecutive days to adult wistar rats caused severe hyperlipidemia characterized by marked increase in serum cholesterol, LDL-C, VLDL-C and triglyceride levels along with an increase in atherogenic index. Serum HDL-C levels were decreased significantly compare to normal control. Pretreatment with Atorvastatin [10 mg/kg, p.o.], CP-1 [25 and 50 mg/kg], CP-2 [25 and 50 mg/kg] and CP-6 [25 and 50 mg/kg] showed significant and dose-dependent protection against dexamethasone and Triton WR-1339-induced hyperlipidemia in rats by maintaining serum total cholesterol, LDL-C, VLDL-C and HDL-C levels within the normal range. Also, a significant decrease in atherogenic index was observed. The anti-hyperlipidemic effect of CP-6 was comparable with reference standard Atorvastatin. Furthermore, CP-6 was found to be more potent than CP-1 and CP-2. These findings suggest that CP-1, CP-2 and CP-6 possess significant anti-hyperlipidemic activity against experimental animal models of hyperlipidemia

Antidiarrheal effect of fractions from stem bark of Thespesia populnea in rodents: Possible antimotility and antisecretory mechanisms

OBJECTIVE@#To evaluate antidiarrheal activity of the fractions of aqueous extract from stem barks of Thespesia populnea (Malvaceae).@*METHODS@#From the aqueous extract three fractions namely ethyl acetate fraction (EAF), methanolic fraction (MF) and residue fraction (RF) were made and studied for antidiarrheal activity. Antidiarrheal activity of the fractions were evaluated in castor oil induced diarrhea, prostaglandin E(2) (PG-E(2)) induced diarrhea and charcoal meal test as in vivo models and the most potent fraction was further evaluated with in vitro models to determine the possible antimotility effect.@*RESULTS@#In castor oil induced diarrhea model, the RF (10, 25, 50 and 100 mg/kg, po.) and MF (100 mg/kg, po.) has significantly reduced the cumulative wet faecal mass, where as the EAF have not shown any significant antidiarrheal activity, RF was found to be more potent than MF. Based on these results and percentage yield, only RF was evaluated in PG-E(2) induced enteropooling and charcoal meal test. RF (10, 25 and 50 mg/kg) had shown significant inhibition of PG-E(2) induced secretions (antisecretory) and decreased the movement of charcoal in charcoal meal test indicating its antimotility activity. Furthermore, RF has showed significant inhibition of acetylcholine, histamine and BaCl(2) induced contractions on rat colon, guinea pig ileum and rabbit jejunum with EC(50) values of 241.7, 303.1 and 286.1 μg/mL, respectively indicating the antimotility effect of RF. The phytochemical analysis of RF showed presence of gums and mucilages and the possible mechanism may be the combination inhibition of elevated prostaglandin biosynthesis and reduced propulsive movement of the intestine.@*CONCLUSIONS@#RF possesses good antidiarrheal activity comparing with other two fractions and the possible mechanism thought to be associated with combination of antisecretory and antimolity.