Effect of Andrographis paniculata Extract on Triglyceride Levels of the Patients with Hypertriglyceridemia: A Randomized Controlled Trial.

BACKGROUND: Hypertriglyceridemia is one of the risk factors for cardiovascular disease, and reduction oftriglyceride (TG) level is recommended in clinical practice guidelines for the treatment. Recently, andrographolide, a main active compound of Andrographispaniculata has been shown to possess hypolipidemic effects in animals. OBJECTIVE: To investigate the TG-lowering effects of A. paniculata extract (APE) in patients with hypertriglyceridemia (TG ≥ 150 mg/dL) using gemfibrozil treatment as the reference. MATERIAL AND METHOD: A randomized controlled clinical trial was carried out in sixty subjects with hypertriglyceridemia. They were divided into three groups and treated with low dose of APE (APE-L, andrographolide 71.64-72.36 mg/day), high dose of APE (APE-H, andrographolide 119.64-120.36 mg/day), and gemfibrozil 300 mg/day. The treatments were conducted for 8 weeks. Guidance on lifestyle modifications was provided. RESULTS: The primary endpoint was the mean difference ± SD (95% CI) in TG levels (baseline from the end of treatment), which were -3 ± 125.6 (-59.1, 58.5), 41.6 ± 86.3 (1.2, 82), and 57.1 ± 94.9 (12.7, 101.6) in the APE-L, APE-H, and gemfibrozil groups, respectively. APE-H 120 mg/day and gemfibrozil 300 mg/day caused a significant reduction of TG level (P = 0.0442 and 0.0145, respectively) when compared to the baseline. There was no notable difference in the safety or tolerability among the treatment groups. CONCLUSION: In patients with modest hypertriglyceridemia with lifestyle intervention, APE-H reduced the TG level comparable to the effect of gemfibrozil 300 mg/day. APE treatment was as tolerable as gemfibrozil treatment. Hence, Andrographis paniculata might be used as an alternative medicine in treating hypertriglyceridemic patients.

Effect of knowledge and perception on adherence to iron and folate supplementation during pregnancy in Kathmandu, Nepal.

BACKGROUND: Adherence to iron and folate supplementation during pregnancy is considered key to prevention and control of iron deficiency anemia. Nepal-like other developing countries-faces problems with adherence vis-a-vis iron/folate supplementation. OBJECTIVE: This descriptive survey aimed to assess the effect ofknowledge and perception ofpregnant women on adherence to iron/folate supplementation in Kathmandu, Nepal. MATERIAL AND METHOD: The present study was conducted in Paropakar Maternity and Womens' Hospital in Kathmandu. Systematic random sampling was used to select 406 persons who were either given a self-administered questionnaire or interviewed. RESULTS: 73.2% of the respondents showed good adherence. Bivariate analysis revealed significant associations between adherence and both knowledge and perception (p<0.05), but through multiple linear regression analysis only perception was found to be statistically associated with adherence (p<0.05). Further multivariate analysis demonstrated that the most important predictors of adherence were: perception of side effects, availability, forgetfulness and reminders from family. CONCLUSION: Adherence to iron/folate supplementation among women during pregnancy needs continuous improvement by minimizing the perception of constraints (viz., side-effects and forgetfulness) and, enhancing availability andfamily support.

Effects of andrographolide on sexual functions, vascular reactivity and serum testosterone level in rodents.

In this study, effects of andrographolide from Andrographis paniculata on sexual functions, vascular reactivity and serum testosterone level in experimental animals were observed. The suspension of andrographolide in 5% DMSO was administered orally at the dose of 50mg/kg to male ICR mice. The female mice involved in mating were made receptive by hormonal treatment. The mating behaviors, mounting latency and mounting frequency, were determined and compared with the standard reference drug sildenafil citrate. Administration of andrographolide significantly decreased the mounting latency at 120 and 180 min and increased mounting frequency at 180 min after treatment. In endothelium-intact rat aortic strips, norepineprine-induced contraction was reduced by preincubation with andrographolide. Administration of 50mg/kg andrographolide orally to male mice once daily for 2, 4, 6 or 8 weeks had no significant effects on sperm morphology and motility. Interestingly, at week 4, serum testosterone level in mice treated with andrographolide was significantly increased when compared to the control. Thus, the effects of andrographolide on vascular response to norepinephrine and testosterone level observed in this study might be contributed to the sexual enhancing properties observed.

Analgesic, antipyretic, anti-inflammatory and toxic effects of andrographolide derivatives in experimental animals.

Andrographolide (1) and 14-deoxy-11,12-didehydroandrographolide (2) are active constituents of Andrographis paniculata (Burm. f.), family Acanthaceae. A. paniculata extracts are reported to have antiviral, antipyretic, immunostimulant and anticancer activities. In this study, 1 and its 14-acetyl- (4) and 3,19-isopropylidenyl- (3) derivatives, as well as 2 and its 3,19-dipalmitoyl-derivative (5), were intraperitoneally tested for their analgesic, antipyretic, anti-inflammatory and acute toxicity effects in animal models. Analgesic effects were tested in mice using hot plate and writhing tests to distinguish the central and peripheral effects, respectively. The results showed that, at 4 mg/kg, all tested substances have significant analgesic effects, and the highest potency was seen with 3, 4 and 5. Increasing the dose of 3 and 5 to 8 mg/kg did not increase the analgesic effect. In the writhing test, 3 and 5, but not 1, showed significant results. In a baker's yeast-induced fever model, 3 and 5 significantly reduced rats' rectal temperature (p < 0.05). In a carrageenan-induced inflammation model, 1, 3 and 5 significantly reduced rats' paw volume. Doses of 3 and 5 up to 100 mg/kg did not show any serious toxic effects. From this study, 3 and 5 are the most interesting derivatives, showing much greater potency than their parent compounds. These could be further developed as analgesic, antipyretic and anti-inflammatory agents, without any serious toxicity.

Purification and characterization of Heteroscorpine-1 (HS-1) toxin from Heterometrus laoticus scorpion venom.

Crude venom from Thai giant scorpion, Heterometrus laoticus, most commonly found in the northeastern area of Thailand, was evaluated for PD50 (paralytic dose 50) activities from abdominal injection to cricket (Gryllus sp.) and activities against various kinds of microorganisms. It exhibited good results in disc diffusion assay for Bacillus subtilis, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus. After purification, toxin showed acceptable results for PD50 determination in entrapped cricket as well as inhibitory activity against B. subtilis, K. pneumoniae, and P. aeruginosa with activities over 300 times higher than that of the crude venom. The purified fraction was showed to contain a single band in SDS-PAGE. MALDI-TOF-MS/MS analysis showed one peak of major protein with 8293Da. Partial amino acid sequence show high homology to Scorpine-a polypeptide toxin family with potassium channel blocking and defensin activity. The novel toxin was named "Heteroscorpine-1" (HS-1) as the first Scorpine from genus Heterometrus. After full length determination by PCR, HS-1 gene was found to be composed of two exons, separated by an intron. Deduction revealed 95 amino acid residues with 19 residues as the leading sequence. It showed about 80% similarity to Panscorpine and Opiscorpine.

Screening of plants acting against Heterometrus laoticus scorpion venom activity on fibroblast cell lysis.

The aqueous extracts of 64 plant species, listed as animal- or insect-bite antidotes in old Thai drug recipes were screened for their activity against fibroblast cell lysis after Heterometrus laoticus scorpion venom treatment. The venom was preincubated with plant extract for 30 min and furthered treated to confluent fibroblast cells for 30 min. More than 40% efficiency (test/control) was obtained from cell treatment with venom preincubated with extracts of Andrographis paniculata Nees (Acanthaceae), Barringtonia acutangula (L.) Gaertn. (Lecythidaceae), Calamus sp. (Palmae), Clinacanthus nutans Lindau (Acanthaceae), Euphorbia neriifolia L. (Euphorbiaceae), Ipomoea aquatica Forssk (Convolvulaceae), Mesua ferrea L. (Guttiferae), Passiflora laurifolia L. (Passifloraceae), Plectranthus amboinicus (Lour.) Spreng. (Labiatae), Ricinus communis L. (Euphorbiaceae), Rumex sp. (Polygonaceae) and Sapindus rarak DC. (Sapindaceae), indicating that they had a tendency to be scorpion venom antidotes. However, only Andrographis paniculata and Barringtonia acutangula extracts provided around 50% viable cells from extract treatments without venom preincubation. These two plant extracts are expected to be scorpion venom antidotes with low cytotoxicity.

Cefazolin induced seizures in hemodialysis patients.

Cephalosporins are epileptogenic drugs, especially when excessive dosages are used or when the drugs are used in patients with decreased renal clearance. The present case report showed that a chronic kidney patient receiving hemodialysis developed generalized tonic clonic seizures when an inappropriate high dose cefazolin was given. Cefazolin 2 g iv q 8 h was given for 25 days continuously to treat fever of unknown origin in a patient who was a severe renal impairment patient. In a severe renal impairment patient, the maintenance dose of cefazolin should be reduced by half and the interval for administration should be extended to 24 h. Even though hemodialysis could remove cefazolin from the blood circulation, in the presented case the very high dose of cefazolin given was far beyond the ability of hemodialysis to clear the drug. The accumulation ofcefazolin, therefore, induced three episodes of seizures on days 14, 21 and 25. More precaution should be taken when prescribing medication to a patient with predisposing factors.

Dose-dependent effects of glutamate in pyridoxine-induced neuropathy.

In order to explore the effects of glutamate in a pyridoxine megadose-induced neuropathy, rats were received glutamate either 0.5 or 1 g/kg/day orally with or without pyridoxine 0.8 g/kg/day intraperitoneally for 14 days. The animal's motor coordination, the muscle power and the thermal threshold were observed daily. The nerve conduction velocity was measured at day 0 and day 15 of the treatment. Glutamate either 0.5 or 1 g/kg/day appeared to have no effect on motor coordination, the nerve conduction velocity and the muscle power score compared with control. However, the thermal response latency was significantly decreased (from day 9) in animals treated with 1 g/kg/day glutamate. In pyridoxine-induced neuropathy rats, glutamate 0.5 g/kg/day significantly decreased the effects of pyridoxine on the sciatic nerve conduction velocity, the muscle power score and the motor coordination. Interestingly, glutamate at a dose of 1 g/kg/day worsened the neurotoxic effects cause by pyridoxine.