Bioactive Markers Based Pharmacokinetic Evaluation of Extracts of a Traditional Medicinal Plant, Piper sarmentosum

In vitro assays are economical and easy to perform but to establish relevance of their results to real clinical outcome in animals or human, pharmacokinetics is prerequisite. Despite various in vitro pharmacological activities of extracts of Piper sarmentosum, there is no report of pharmacokinetics. Therefore, the present study aimed to evaluate ethanol extract of fruit of the plant in dose of 500 mg kg−1 orally for pharmacokinetics. Sprague-Dawley rats were randomly divided into groups 1, 2, and 3 (each n = 6) to study absorption, distribution and excretion, respectively. High performance liquid chromatography (HPLC) with ultraviolet detection was applied to quantify pellitorine, sarmentine and sarmentosine in plasma, tissues, feces and urine to calculate pharmacokinetic parameters. Pellitorine exhibited maximum plasma concentration (Cmax) 34.77 ng mL−1 ± 1.040, time to achieve Cmax (Tmax) 8 h, mean resident time (MRT) 26.00 ± 0.149 h and half life (t1/2) 18.64 ± 1.65 h. Sarmentine showed Cmax 191.50 ± 12.69 ng mL−1, Tmax 6 h, MRT 11.12 ± 0.44 h and t1/2 10.30 ± 1.98 h. Sarmentosine exhibited zero oral bioavailability because it was neither detected in plasma nor in tissues, and in urine. Pellitorine was found to be distributed in intestinal wall, liver, lungs, kidney, and heart, whereas sarmentine was found only in intestinal wall and heart. The cumulative excretion of pellitorine, sarmentine and sarmentosine in feces in 72 h was 0.0773, 0.976, and 0.438 μg, respectively. This study shows that pellitorine and sarmentine have good oral bioavailability while sarmentosine is not absorbed from the gastrointestinal tract

Evaluation of ethanol extracts of leaves and fruit of Piper sarmentosum for in vivo hepatoprotective activity

The present study is aimed to describe hepatoprotective activity of extracts of a medicinal plant, Piper sarmentosum, in rats against CCl4-induced toxicity. Seven groups of Sprague Dawley rats each containing six animals were treated as: group I (CCl4), group II (control), group III and IV (fruit extract 500 and 250 mg/kg, respectively), group V and VI (leaf extract 500 and 250 mg/kg, respectively) and group VII (vitamin-E). The extracts and vitamin-E were administered orally for 14 days whilst equivalent amount of sample vehicle was administered to CCl4 and control groups. Four hour following the last dose, a single dose of CCl4 (1.5 mg/kg, 1:1 olive oil) was administered orally to animals of all the groups except control. After 24 h blood was collected for the determination of hepatic function markers, and the animals were sacrificed to get liver for histology. Comparison of hepatic function markers and histology of pretreated and CCl4 groups indicated that both the extracts in the two doses had protected liver from CCl4 toxicity (P < 0.05). It is concluded from the present study that use of the plant as a vegetable or in the form of extracts may be valuable to protect liver from oxidative stress in hepatitis and long-term therapyColegio de Farmacéuticos de la Provincia de Buenos Aire

Interaction of isoniazid with Mycobacterium tuberculosis enoyl-acyl carrier protein reductase (InhA): from bioinformatics perspective.

Tuberculosis (TB), caused by Mycobacterium tuberculosis is a leading killer that has plagued mankind for centuries. The disease is estimated to infect 8 million and kill 2 - 3 million people each year (Rouse et al., 1995; Manca et al., 1997). A frequently used drug to treat TB is isonicotinic acid hydrazide (INH/ isoniazid) but unfortunately, INHresistant M. tuberculosis organisms are becoming quite common now

Anti-diabetic activity-guided screening of aqueous-ethanol Moringa oleifera extracts and fractions: Identification of marker compounds

Purpose: To explore the anti-diabetic effects of Moringa oleifera extracts and  fractions, and to identify their active/marker compounds.Methods: Five different aqueous ethanol extracts (95, 75, 50, 25 %v/v and 100 % water) of Moringa oleifera were given orally to normal rats to assess their hypoglycemic activities and effect on intraperitoneal glucose tolerance test (IPGTT) data. Rats with streptozotocin-induced diabetes were used to assess acute and sub-chronic anti-hyperglycemic activities. The most active extract was further subjected to liquid-liquid fractionation into hexane, chloroform, ethyl acetate,  butanol, and water; these fractions were screened for anti-diabetic activities. The most active extract, and fractions thereof, were then subjected to qualitative and quantitative phytochemical analysis. Standardization was achieved via thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC), and used to identify marker compounds.Results: Of all the extracts and fractions, 95 % (v/v) ethanol extract (at 1,000 mg/kg) and the butanol fraction thereof (at 500 mg/kg) were the most active,  reducing blood glucose concentration after onetime (acute) administration to  diabetic rats (p &lt; 0.01). No significant hypoglycemic activity was apparent, and the materials had no effect on IPGTT performance by normal rats. TLC and HPLC  identified quercetin 3-β-D-glucoside, kaempferol-3-O-glucoside, and cryptochlorogenic acid.Conclusion: An M. oleifera leaf extract exhibited anti-hyperglycaemic activity in diabetic rats only. This effect was likely attributable to cryptochlorogenic acid, quercetin 3-β-D-glucoside, and kaempferol 3-Oglucoside. Keywords: Anti-diabetic, Moringa oleifera, Cryptochlorogenic acid, Quercetin 3-β-D-glucoside, Kaempferol 3-O-glucoside, Streptozotoci

(E)-N′-[(E)-3-(4-Hydr­oxy-3-methoxy­phen­yl)allyl­idene]isonicotinohydrazide

In the title compound, C16H15N3O3, the dihedral angle between the pyridine and benzene rings is 7.66 (5)°. The crystal packing is consolidated by inter­molecular C—H⋯O and O—H⋯N inter­actions, which link the mol­ecules into zigzag chains propagating along [010]. The chains are further linked into a three-dimensional network by N—H⋯O, C—H⋯N, C—H⋯O and C—H⋯π inter­actions

Evaluation of orthosiphon stamineus aqueous extract for in vitro antimycobacterial activity and its interaction with isoniazid

In addition to a number of traditional medicinal uses, recently the consumption of leaves of Orthosiphon stamineus infusion (Misai kuching Tea and Java Tea) has gained popularity in many countries such as Malaysia, Indonesia and Thailand. The plant is known to have antioxidant activities and some constituents possessing antimycobacterial activity, hence may have interaction with isoniazid (INH), an anti-TB drug acting through free radicals. Therefore, the present study aims to investigate a standardized aqueous extract of the plant and some of its fractions for antimycobacterial activity and to evaluate potential interaction with INH. Using HPLC, total contents of betulinic, oleanolic and ursolic acids in the extract, hexane (HF), chloroform (CF) and ethyl acetate fractions (EA) were found to be 0.016, 0.62, 0.183 and 0.00 mg/g, respectively. In antimycobacterial assays, the minimum inhibitory concentrations (MICs) of the extract, HF, CF and INH were found to be 25.00, 3.12, 6.25 and 0.39 μg/mL, respectively. The combinations of the extract as well as the fractions with INH -in various proportions- exhibited fractional inhibitory concentration index (FICI) > 0.5 and ≤ 4, which indicated no statistically significant interaction. The results of the present study indicate that aqueous extracts of the plant have no significant interaction with INH.Colegio de Farmacéuticos de la Provincia de Buenos Aire

(E)-N′-(2,4,6-Trimethyl­benzyl­idene)isonicotinohydrazide

The title isoniazid derivative, C16H17N3O, exists in an E configuration with respect to the Schiff base C=N bond. The pyridine ring is essentially planar [maximum deviation = 0.009 (3) Å]. The mean plane through the hydrazide unit forms dihedral angles of 38.38 (16) and 39.42 (16)°, respectively, with the pyridine and benzene rings. In the crystal structure, symmetry-related mol­ecules are linked via inter­molecular N—H⋯O hydrogen bonds into chains along [100]. The crystal structure is further stabilized by weak inter­molecular C—H⋯π inter­actions

(E)-N′-(2-Benzyl­oxybenzyl­idene)isonicotinohydrazide methanol solvate monohydrate

The title compound, C20H17N3O2·CH4O·H2O, was synthesized by the condensation reaction of 2-benzyl­oxybenzaldehyde with isoniazid (isonicotinic acid hydrazide). The tricyclic compound displays a trans configuration with respect to the C=N double bond. The central benzene ring makes dihedral angles of 8.83 (7) and 70.39 (8)° with the pyridine ring and the terminal benzene ring, respectively. The dihedral angle between the pyridine ring and the terminal benzene ring is 73.11 (8)°. In the crystal structure, mol­ecules are connected by inter­molecular N—H⋯O, O—H⋯O, O—H⋯(N,N) and C—H⋯O hydrogen bonds, forming a two-dimensional network perpendicular to the a axis

(E)-N’-(2,3,4-Trimethoxy­benzyl­idene)isonicotinohydrazide

In the title compound, C16H17N3O4, the mol­ecule exists in an E configuration with respect to the C=N double bond. The mol­ecule is not planar, the dihedral angle between the pyridine and benzene rings being 71.67 (8)°. In the crystal structure, mol­ecules are linked into chains along the b axis by bifurcated N—H⋯O and C—H⋯O hydrogen bonds. These chains are linked into a three-dimensional network by C—H⋯O and C—H⋯π inter­actions